diff --git a/.github/workflows/run-tests.yml b/.github/workflows/run-tests.yml
index 1d7a08699..87361445d 100644
--- a/.github/workflows/run-tests.yml
+++ b/.github/workflows/run-tests.yml
@@ -68,6 +68,9 @@ jobs:
           - os: ubuntu-latest
             python: '3.11'
             mode: nfs
+          - os: ubuntu-latest
+            python: '3.11'
+            mode: lowest-deps
 
     steps:
     - name: Set up environment
@@ -83,10 +86,17 @@ jobs:
         python-version: ${{ matrix.python }}
 
     - name: Install dependencies
+      if: matrix.mode != 'lowest-deps'
       run: |
         python -m pip install --upgrade pip wheel
         pip install ".[extras,test]"
 
+    - name: Install tox for lowest-deps mode
+      if: matrix.mode == 'lowest-deps'
+      run: |
+        python -m pip install --upgrade pip
+        pip install "tox>=4" "tox-uv>=1.11"
+
     # Set only if matrix.instance_name is defined
     - name: Set DANDI_TESTS_INSTANCE_NAME
       if: ${{ matrix.instance_name }}
@@ -129,10 +139,15 @@ jobs:
       run: echo PYTEST_ADDOPTS=--scheduled >> "$GITHUB_ENV"
 
     - name: Run all tests except those involving obolibrary
-      if: matrix.mode != 'dandi-api' && matrix.mode != 'obolibrary-only'
+      if: matrix.mode != 'dandi-api' && matrix.mode != 'obolibrary-only' && matrix.mode != 'lowest-deps'
       run: |
         python -m pytest -s -v -m "not obolibrary" --cov=dandi --cov-report=xml dandi
 
+    - name: Run tests against minimum declared dependency versions
+      if: matrix.mode == 'lowest-deps'
+      run: |
+        tox -e py3-lowest -- -s -m "not obolibrary"
+
     - name: Run only tests related to obolibrary
       if: matrix.mode == 'obolibrary-only'
       run: |
diff --git a/.gitignore b/.gitignore
index b39d66477..e2d2dab22 100644
--- a/.gitignore
+++ b/.gitignore
@@ -20,3 +20,4 @@ sandbox/
 venv/
 venvs/
 .DS_Store
+.duct
diff --git a/pyproject.toml b/pyproject.toml
index 03d9f0d62..bc00d6ac6 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -46,36 +46,43 @@ dependencies = [
     "bidsschematools ~= 1.0",
     "bids-validator-deno >= 2.0.5",
     "click >= 8.2",
-    "click-didyoumean",
+    "click-didyoumean >= 0.3.1",
     "dandischema ~= 0.12.0",
     "etelemetry >= 0.2.2",
-    "fasteners",
+    "fasteners >= 0.19",
     "fscacher >= 0.3.0",
-    # 3.14.4: https://github.com/hdmf-dev/hdmf/issues/1186
-    "hdmf != 3.5.0,!=3.14.4",
-    "humanize",
+    # Floor raised to what `py3-lowest` actually resolves: modern pynwb pins
+    # hdmf >= 4, so declared floor is now the tested floor.
+    "hdmf >= 4.1.0",
+    "humanize >= 4.5.0",
     "interleave ~= 0.3",
-    "joblib",
-    "keyring != 23.9.0",
-    "keyrings.alt",
-    "packaging",
-    "platformdirs",
-    "pycryptodomex",  # for EncryptedKeyring backend in keyrings.alt
-    "pydantic ~= 2.0",
-    "pynwb >= 1.0.3,!=1.1.0,!=2.3.0",
-    "numcodecs",
+    "joblib >= 1.3.0",
+    "keyring >= 23.10.0",
+    "keyrings.alt >= 5.0.0",
+    "packaging >= 22.0",
+    # Floor raised: keyring 23.10 chain (jaraco.classes) transitively requires >= 4.
+    "platformdirs >= 4.1.0",
+    "pycryptodomex >= 3.16.0",  # for EncryptedKeyring backend in keyrings.alt
+    "pydantic ~= 2.9",
+    # Floor raised: dandischema 0.12 / nwbinspector 0.7 require modern pynwb.
+    "pynwb >= 3.1.0",
+    "numcodecs >= 0.11.0",
     "nwbinspector >= 0.7.0",
-    "pyout >=0.5, !=0.6.0",
-    "python-dateutil",
-    "requests ~= 2.20",
-    "ruamel.yaml >=0.15, <1",
-    "semantic-version",
-    "tenacity",
-    "tensorstore",
+    "pyout >= 0.7.3",
+    "python-dateutil >= 2.9.0",
+    # Floor raised: urllib3 2.x requires requests >= 2.30.
+    "requests ~= 2.30",
+    # Floor raised: modern hdmf/pynwb chain requires >= 0.16.
+    "ruamel.yaml >= 0.16.0, < 1",
+    "semantic-version >= 2.10.0",
+    "tenacity >= 8.2.0",
+    # 0.1.62 first release built for numpy 2.x
+    "tensorstore >= 0.1.62",
     # possibly silently incomplete downloads: https://github.com/dandi/dandi-cli/issues/1500
-    "urllib3 >= 2.0.0",
-    "yarl ~= 1.9",
-    "zarr >= 2.10, <= 3.1.5",
+    "urllib3 >= 2.0.2",
+    "yarl >= 1.9.1, < 2",
+    # Floor raised: numcodecs 0.11 / hdmf-zarr chain requires >= 2.18.
+    "zarr >= 2.18.0, <= 3.1.5",
     "zarr_checksum ~= 0.4.0",
 ]
 dynamic = ["version"]
@@ -89,23 +96,25 @@ extensions = [
     "ndx-events",
 ]
 extras = [
-    "duecredit >= 0.6.0",
-    "fsspec[http]",
+    "duecredit >= 0.9.2",
+    "fsspec[http] >= 2022.11.0",
 ]
 test = [
-    "aiohttp < 3.14",  # See https://github.com/kevin1024/vcrpy/issues/995
-    "anys ~= 0.2",
-    "coverage",
+    "aiohttp >= 3.8.4, < 3.14",  # See https://github.com/kevin1024/vcrpy/issues/995
+    "anys ~= 0.3",
+    "coverage >= 7.0.0",
+    # 4.10.0.84 first built for numpy 2.x ABI (older wheels segfault under numpy 2)
     # Workaround for VideoWriter regression in 4.13.0.90 on Intel macOS
-    "opencv-python < 4.13 ; sys_platform == 'darwin' and platform_machine != 'arm64'",
-    "opencv-python ; sys_platform != 'darwin' or platform_machine == 'arm64'",
-    "pytest",
-    "pytest-cov",
-    "pytest-mock",
-    "pytest-rerunfailures",
-    "pytest-timeout",
-    "responses != 0.24.0, != 0.25.5",
-    "vcrpy",
+    "opencv-python >= 4.10.0.84, < 4.13 ; sys_platform == 'darwin' and platform_machine != 'arm64'",
+    "opencv-python >= 4.10.0.84 ; sys_platform != 'darwin' or platform_machine == 'arm64'",
+    "pytest >= 7.2.0",
+    "pytest-cov >= 4.1.0",
+    "pytest-mock >= 3.11.0",
+    "pytest-rerunfailures >= 10.3",
+    "pytest-timeout >= 2.2.0",
+    "responses >= 0.23.0, != 0.24.0, != 0.25.5",
+    # 5.0 switched to urllib3.connection.VerifiedHTTPSConnection (urllib3 2.x compat)
+    "vcrpy >= 5.0.0",
 ]
 tools = [
     "boto3",
diff --git a/tox.ini b/tox.ini
index b71a3efcf..97cf30772 100644
--- a/tox.ini
+++ b/tox.ini
@@ -1,4 +1,6 @@
 [tox]
+requires =
+    tox-uv >= 1.11
 envlist = lint,typing,py3
 
 [testenv]
@@ -16,6 +18,19 @@ commands =
     coverage combine
     coverage report
 
+# Install the lowest declared-compatible version of every direct dependency
+# (via uv's `lowest-direct` resolution) on the minimum supported Python.
+# Purpose: verify that the lower bounds in pyproject.toml are actually valid.
+# Any direct dep without a lower bound will resolve to its oldest release and
+# will almost certainly break; that failure is a signal to add a real bound.
+[testenv:py3-lowest]
+basepython = python3.11
+uv_resolution = lowest-direct
+setenv = {[testenv]setenv}
+passenv = {[testenv]passenv}
+extras = {[testenv]extras}
+commands = {[testenv]commands}
+
 [testenv:lint]
 skip_install = true
 deps =