diff --git a/.github/workflows/test.yml b/.github/workflows/test.yml
index da065f340..253726362 100644
--- a/.github/workflows/test.yml
+++ b/.github/workflows/test.yml
@@ -17,6 +17,7 @@ jobs:
       - uses: astral-sh/setup-uv@v7
         with:
           python-version: "3.11"
+      - uses: dtolnay/rust-toolchain@1.95.0 # pinned; keep in sync with rust-toolchain.toml
       - run: uv sync --frozen
       - run: PYTHONPATH=. uv run pytest --collect-only -q
       - run: PYTHONPATH=. uv run pytest -m unit --no-cov -q
@@ -34,5 +35,6 @@ jobs:
       - uses: astral-sh/setup-uv@v7
         with:
           python-version: "3.11"
+      - uses: dtolnay/rust-toolchain@1.95.0 # pinned; keep in sync with rust-toolchain.toml
       - run: uv sync --frozen
       - run: PYTHONPATH=. uv run pytest --network -m "unit or network or slow" --no-cov -q
diff --git a/.gitignore b/.gitignore
index 36e021879..adbc5b9c8 100644
--- a/.gitignore
+++ b/.gitignore
@@ -36,3 +36,10 @@ docs/sources/*/impact-report/modified-cliques.json
 .coverage
 .coverage.*
 htmlcov/
+
+# maturin / Rust build artifacts
+rust/target/
+# native extension dropped into src/ by `maturin develop` (don't commit compiled binaries)
+src/rs.*.so
+src/rs.*.pyd
+src/rs.*.dylib
diff --git a/Dockerfile b/Dockerfile
index ae4fdd4ee..4a5bcb806 100644
--- a/Dockerfile
+++ b/Dockerfile
@@ -36,13 +36,18 @@ RUN adduser --home ${ROOT} --uid 1000 nru
 # Set up a $ROOT directory with the source code to work in.
 RUN mkdir -p ${ROOT}
 WORKDIR ${ROOT}
+
+# Rust toolchain — required because the build backend is maturin (compiles a native extension).
+RUN apt-get update && apt-get install -y cargo
+
 USER nru
 COPY --chown=nru . ${ROOT}
 
-# Install and run `uv sync` to install packages.
+# Install uv and sync packages. `--frozen` installs exactly the committed uv.lock
+# (no re-resolution), keeping the image reproducible and matching CI's `uv sync --frozen`.
 RUN pipx install uv
 ENV PATH="${ROOT}/.local/bin:${PATH}"
-RUN uv sync
+RUN uv sync --frozen
 
 # Our default entrypoint is to start the Babel run.
 ENTRYPOINT ["bash", "-c", "uv run snakemake --cores ${CORES}"]
diff --git a/pyproject.toml b/pyproject.toml
index 63b17de88..84d610865 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -39,6 +39,7 @@ Issues = "https://github.com/NCATSTranslator/Babel/issues"
 [dependency-groups]
 dev = [
     "ipykernel>=7.1.0",
+    "maturin>=1.0,<2.0",
     "py-spy>=0.4.2",
     "ruff>=0.14.14",
     "rumdl>=0.2.4",
@@ -55,12 +56,16 @@ source-impact-report = "src.tools.source_impact_report.cli:main"
 package = true
 
 [build-system]
-requires = ["setuptools>=83.0.0"]
-build-backend = "setuptools.build_meta"
+requires = ["maturin>=1.0,<2.0"]
+build-backend = "maturin"
 
-[tool.setuptools.packages.find]
-where = ["."]
-include = ["src", "src.*"]
+[tool.maturin]
+# The importable Python package is literally named `src` (flat layout). A dotted module-name
+# places the compiled extension at `src/rs.*` and tells maturin the package to bundle is `src`
+# (auto-resolved to the repo root since src-layout detection won't fire).
+module-name = "src.rs"
+# Rust source lives under rust/ so Cargo never collides with the Python `src/` dir.
+manifest-path = "rust/Cargo.toml"
 
 
 # Linting/formatting configuration
@@ -84,6 +89,13 @@ ignore = [
 fixable = ["ALL"]
 unfixable = []
 
+[tool.ruff.format]
+# Ruff 0.16.0 began formatting Python code fences inside Markdown, which overlaps with the
+# dedicated rumdl Markdown check and broke CI when astral-sh/ruff-action@v3 floated to 0.16.0
+# (pyproject pins only a floor, >=0.14.14). Keep ruff's formatter scoped to Python source and
+# leave Markdown to rumdl so formatting CI stays deterministic across ruff releases.
+exclude = ["*.md"]
+
 [tool.snakefmt]
 line_length = 120
 include = '\.snakefile$|^Snakefile'
diff --git a/rust-toolchain.toml b/rust-toolchain.toml
new file mode 100644
index 000000000..c62df1bcc
--- /dev/null
+++ b/rust-toolchain.toml
@@ -0,0 +1,6 @@
+# Pin the Rust toolchain so local builds, CI, and any rustup-based environment all
+# compile the maturin/PyO3 extension with the same compiler version. The CI action ref
+# (dtolnay/rust-toolchain in .github/workflows/test.yml) is pinned to match this; bump
+# both together when upgrading Rust.
+[toolchain]
+channel = "1.95.0"
diff --git a/rust/Cargo.lock b/rust/Cargo.lock
new file mode 100644
index 000000000..76ba98f35
--- /dev/null
+++ b/rust/Cargo.lock
@@ -0,0 +1,180 @@
+# This file is automatically @generated by Cargo.
+# It is not intended for manual editing.
+version = 4
+
+[[package]]
+name = "autocfg"
+version = "1.5.1"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "f2032f911046de80f0a198e0901378627c33f59ea0ac00e363d481118bd70a53"
+
+[[package]]
+name = "babel-pipeline"
+version = "1.17.0"
+dependencies = [
+ "pyo3",
+]
+
+[[package]]
+name = "cfg-if"
+version = "1.0.4"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "9330f8b2ff13f34540b44e946ef35111825727b38d33286ef986142615121801"
+
+[[package]]
+name = "heck"
+version = "0.5.0"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "2304e00983f87ffb38b55b444b5e3b60a884b5d30c0fca7d82fe33449bbe55ea"
+
+[[package]]
+name = "indoc"
+version = "2.0.7"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "79cf5c93f93228cf8efb3ba362535fb11199ac548a09ce117c9b1adc3030d706"
+dependencies = [
+ "rustversion",
+]
+
+[[package]]
+name = "libc"
+version = "0.2.189"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "3eaf3ede3fee6db1a4c2ee091bf8a8b4dccdc6d17f656fb07896ee72867612f2"
+
+[[package]]
+name = "memoffset"
+version = "0.9.1"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "488016bfae457b036d996092f6cb448677611ce4449e970ceaf42695203f218a"
+dependencies = [
+ "autocfg",
+]
+
+[[package]]
+name = "once_cell"
+version = "1.21.4"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "9f7c3e4beb33f85d45ae3e3a1792185706c8e16d043238c593331cc7cd313b50"
+
+[[package]]
+name = "portable-atomic"
+version = "1.14.0"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "3d20d5497ef88037a52ff98267d066e7f11fcc5e99bbfbd58a42336193aacec3"
+
+[[package]]
+name = "proc-macro2"
+version = "1.0.107"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "985e7ec9bb745e6ce6535b544d84d6cd6f7ad8bd711c398938ae983b91a766d9"
+dependencies = [
+ "unicode-ident",
+]
+
+[[package]]
+name = "pyo3"
+version = "0.23.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "7778bffd85cf38175ac1f545509665d0b9b92a198ca7941f131f85f7a4f9a872"
+dependencies = [
+ "cfg-if",
+ "indoc",
+ "libc",
+ "memoffset",
+ "once_cell",
+ "portable-atomic",
+ "pyo3-build-config",
+ "pyo3-ffi",
+ "pyo3-macros",
+ "unindent",
+]
+
+[[package]]
+name = "pyo3-build-config"
+version = "0.23.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "94f6cbe86ef3bf18998d9df6e0f3fc1050a8c5efa409bf712e661a4366e010fb"
+dependencies = [
+ "once_cell",
+ "target-lexicon",
+]
+
+[[package]]
+name = "pyo3-ffi"
+version = "0.23.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "e9f1b4c431c0bb1c8fb0a338709859eed0d030ff6daa34368d3b152a63dfdd8d"
+dependencies = [
+ "libc",
+ "pyo3-build-config",
+]
+
+[[package]]
+name = "pyo3-macros"
+version = "0.23.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "fbc2201328f63c4710f68abdf653c89d8dbc2858b88c5d88b0ff38a75288a9da"
+dependencies = [
+ "proc-macro2",
+ "pyo3-macros-backend",
+ "quote",
+ "syn",
+]
+
+[[package]]
+name = "pyo3-macros-backend"
+version = "0.23.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "fca6726ad0f3da9c9de093d6f116a93c1a38e417ed73bf138472cf4064f72028"
+dependencies = [
+ "heck",
+ "proc-macro2",
+ "pyo3-build-config",
+ "quote",
+ "syn",
+]
+
+[[package]]
+name = "quote"
+version = "1.0.47"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "1fbf4db142a473a8d80c26bbf18454ed458bf8d26c8219c331daecfdbd079001"
+dependencies = [
+ "proc-macro2",
+]
+
+[[package]]
+name = "rustversion"
+version = "1.0.23"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "cf54715a573b99ac80df0bc206da022bcd442c974952c7b9720069370852e21f"
+
+[[package]]
+name = "syn"
+version = "2.0.119"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "872831b642d1a07999a962a351ed35b955ea2cfc8f3862091e2a240a84f17297"
+dependencies = [
+ "proc-macro2",
+ "quote",
+ "unicode-ident",
+]
+
+[[package]]
+name = "target-lexicon"
+version = "0.12.16"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "61c41af27dd6d1e27b1b16b489db798443478cef1f06a660c96db617ba5de3b1"
+
+[[package]]
+name = "unicode-ident"
+version = "1.0.24"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "e6e4313cd5fcd3dad5cafa179702e2b244f760991f45397d14d4ebf38247da75"
+
+[[package]]
+name = "unindent"
+version = "0.2.4"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "7264e107f553ccae879d21fbea1d6724ac785e8c3bfc762137959b5802826ef3"
diff --git a/rust/Cargo.toml b/rust/Cargo.toml
new file mode 100644
index 000000000..426067dda
--- /dev/null
+++ b/rust/Cargo.toml
@@ -0,0 +1,11 @@
+[package]
+name = "babel-pipeline"
+version = "1.17.0"   # valid SemVer (3 parts); published version is "1.17" from root pyproject
+edition = "2021"
+
+[lib]
+name = "rs"                   # matches the #[pymodule] fn + module-name's last component
+crate-type = ["cdylib"]
+
+[dependencies]
+pyo3 = { version = "0.23", features = ["abi3-py311", "extension-module"] }
diff --git a/rust/src/lib.rs b/rust/src/lib.rs
new file mode 100644
index 000000000..0db123630
--- /dev/null
+++ b/rust/src/lib.rs
@@ -0,0 +1,13 @@
+//! Placeholder native extension for babel-pipeline.
+//!
+//! The build backend is maturin; this empty module exists only so the project builds as a
+//! mixed Rust/Python package. Real functionality will land in a follow-up PR.
+
+use pyo3::prelude::*;
+
+/// Empty pyo3 module, importable as `from src import rs`. Name must match the last component
+/// of `[tool.maturin] module-name` ("src.rs" → `rs`).
+#[pymodule]
+fn rs(_m: &Bound<'_, PyModule>) -> PyResult<()> {
+    Ok(())
+}
diff --git a/uv.lock b/uv.lock
index 1502a8e5c..de33fc912 100644
--- a/uv.lock
+++ b/uv.lock
@@ -211,6 +211,7 @@ dependencies = [
 [package.dev-dependencies]
 dev = [
     { name = "ipykernel" },
+    { name = "maturin" },
     { name = "py-spy" },
     { name = "ruff" },
     { name = "rumdl" },
@@ -247,6 +248,7 @@ requires-dist = [
 [package.metadata.requires-dev]
 dev = [
     { name = "ipykernel", specifier = ">=7.1.0" },
+    { name = "maturin", specifier = ">=1.0,<2.0" },
     { name = "py-spy", specifier = ">=0.4.2" },
     { name = "ruff", specifier = ">=0.14.14" },
     { name = "rumdl", specifier = ">=0.2.4" },
@@ -1239,6 +1241,27 @@ wheels = [
     { url = "https://files.pythonhosted.org/packages/41/09/5b161152e2d90f7b87f781c2e1267494aef9c32498df793f73ad0a0a494a/matplotlib_inline-0.2.2-py3-none-any.whl", hash = "sha256:3c821cf1c209f59fb2d2d64abbf5b23b67bcb2210d663f9918dd851c6da1fcf6", size = 9534, upload-time = "2026-05-08T17:33:32.055Z" },
 ]
 
+[[package]]
+name = "maturin"
+version = "1.14.1"
+source = { registry = "https://pypi.org/simple" }
+sdist = { url = "https://files.pythonhosted.org/packages/e7/b3/addd877f871fb1860d46d3a4f206ecb10b946c85846805e6367631926fd3/maturin-1.14.1.tar.gz", hash = "sha256:9d6577a62cd08e0ceba7a0db06fb098e0c9b1b3429bad747a4f3a18215a1b3df", size = 369637, upload-time = "2026-06-19T05:19:49.774Z" }
+wheels = [
+    { url = "https://files.pythonhosted.org/packages/f4/f0/97c5a5bd9c71653a066c0976a484eaaae50b9369557838a4176b7b0bdaa5/maturin-1.14.1-py3-none-linux_armv6l.whl", hash = "sha256:522292398945442cdafa9daeb2271b2340fbde57027b818f923f88eab04174f8", size = 10207496, upload-time = "2026-06-19T05:19:09.321Z" },
+    { url = "https://files.pythonhosted.org/packages/fe/83/294bca639b0e052f1e2f65199b3db258780c7d4e31408b934c9c974a1379/maturin-1.14.1-py3-none-macosx_10_12_x86_64.macosx_11_0_arm64.macosx_10_12_universal2.whl", hash = "sha256:ffe5ad71f21d1e6603c4dd75f7fee34adf5ed5ebcebb692886549888ebb329ed", size = 19680113, upload-time = "2026-06-19T05:19:13.43Z" },
+    { url = "https://files.pythonhosted.org/packages/43/b6/79c881410a3b1c187f7eb3d407aecae646c6a4433d630d72200359015e83/maturin-1.14.1-py3-none-macosx_10_12_x86_64.whl", hash = "sha256:f3306078070c1508fd715b9116070cbcaff5959024272a9f1e6f5cb29768b86c", size = 10169205, upload-time = "2026-06-19T05:19:16.615Z" },
+    { url = "https://files.pythonhosted.org/packages/93/9d/44b6f26dcb7f7a04c5501ac2dbb6ca1490150682baa525ca5860504f9eab/maturin-1.14.1-py3-none-manylinux_2_12_i686.manylinux2010_i686.musllinux_1_1_i686.whl", hash = "sha256:cd457cd88961156e26379e1155bd287cc0ec1c8b2f1582b0660fb31b87c8842d", size = 10188098, upload-time = "2026-06-19T05:19:19.736Z" },
+    { url = "https://files.pythonhosted.org/packages/1a/bd/9c0d5d6983905ce2c9edaa073a7e89355a9cf7f396988e05d32f1c37785d/maturin-1.14.1-py3-none-manylinux_2_12_x86_64.manylinux2010_x86_64.musllinux_1_1_x86_64.whl", hash = "sha256:dfc54ae32e6fcb18302193ab9a30b0b25eefffba994ae13238974805533ef75e", size = 10627576, upload-time = "2026-06-19T05:19:22.713Z" },
+    { url = "https://files.pythonhosted.org/packages/e5/33/b096412bd6a7cb399652b260666f901adf88a687181a6dbd6a3f89f0a94e/maturin-1.14.1-py3-none-manylinux_2_17_aarch64.manylinux2014_aarch64.musllinux_1_1_aarch64.whl", hash = "sha256:a131d912b5267e640bc96d70f4914e10590aed64082ec9abacba7cea52004224", size = 10085181, upload-time = "2026-06-19T05:19:25.69Z" },
+    { url = "https://files.pythonhosted.org/packages/56/8d/08c3bf469c38a23c9e6c877e338193001eb604d010fedc08341974e38528/maturin-1.14.1-py3-none-manylinux_2_17_armv7l.manylinux2014_armv7l.musllinux_1_1_armv7l.whl", hash = "sha256:be18fc568fb76884c0205456336892a75105ec398e6b667cd777c6268bd06d69", size = 10026363, upload-time = "2026-06-19T05:19:28.904Z" },
+    { url = "https://files.pythonhosted.org/packages/3a/a4/c4d1a92839f8745ab4aab988a7db884a79d6d710bd3b286fcf9316dece1a/maturin-1.14.1-py3-none-manylinux_2_17_ppc64le.manylinux2014_ppc64le.musllinux_1_1_ppc64le.whl", hash = "sha256:994a0c8ba3ad8a92b3a9ee1b02645d200d610216b15cff5102b0fe65e8e08666", size = 13321347, upload-time = "2026-06-19T05:19:32.411Z" },
+    { url = "https://files.pythonhosted.org/packages/b3/fa/170f04624d03fd07d2a8b1b67de83a127af93aef9eaa425839553347297b/maturin-1.14.1-py3-none-manylinux_2_17_s390x.manylinux2014_s390x.whl", hash = "sha256:be80866363e605d137991b491a741a84cde9ae350183c4c85f49690ca9aaaa65", size = 10877609, upload-time = "2026-06-19T05:19:35.448Z" },
+    { url = "https://files.pythonhosted.org/packages/61/ad/1ae2e1d0ded282bf2c55ac13f0811d87deb425e200ae64a15785675dede9/maturin-1.14.1-py3-none-manylinux_2_31_riscv64.musllinux_1_1_riscv64.whl", hash = "sha256:5282dffd4b539d2be245f4e5b1a5ab6bc1033b58f4a4872f5833f9d43c954aa4", size = 10417316, upload-time = "2026-06-19T05:19:38.28Z" },
+    { url = "https://files.pythonhosted.org/packages/fb/27/bf677183920718da49cd7982d6a3ffc440aad8919329f571d189f81b7bdf/maturin-1.14.1-py3-none-win32.whl", hash = "sha256:1a04de0a20188f95c721b5702eed18140bdcccb28c386797093eca3f62f4d4e0", size = 8931293, upload-time = "2026-06-19T05:19:41.183Z" },
+    { url = "https://files.pythonhosted.org/packages/63/4b/585adeb9167b08d3cdff0032a938b0e72655c92003df4f52c3f696a1bcc2/maturin-1.14.1-py3-none-win_amd64.whl", hash = "sha256:3c9f94640ecc4895e94abaf834a0684430032c865b2748a36c12461fd9252fdd", size = 10314067, upload-time = "2026-06-19T05:19:44.389Z" },
+    { url = "https://files.pythonhosted.org/packages/51/d4/dac8c0720ae246be1700afb6fbdbbea20fe35b13f6570b2f70faa005df77/maturin-1.14.1-py3-none-win_arm64.whl", hash = "sha256:15cea8fcb3ba47dd636f50092bb34baea8b04ac777392f23e6bf8a9a61efb894", size = 9718943, upload-time = "2026-06-19T05:19:47.49Z" },
+]
+
 [[package]]
 name = "more-itertools"
 version = "11.1.0"