HS3ST1 encodes heparan sulfate-glucosamine 3-sulfotransferase 1, which catalyzes the rate-limiting step in biosynthesis of anticoagulant heparan sulfate by transferring sulfate groups to position 3 of glucosamine residues 12. This modification is crucial for creating the antithrombin pentasaccharide binding site, generating antithrombin-binding heparan sulfate (HSAT+) that mediates antithrombin's anti-inflammatory activities 34. HS3ST1 expression is ubiquitous in epithelial cell basement membranes and plays important roles in tumor biology 4. In colorectal cancer, HS3ST1 is highly expressed in late-stage tumor-infiltrating immune cells and promotes tumor growth 5. Conversely, in pancreatic cancer, HS3ST1 expression decreases during malignant progression, and its loss promotes inflammation, suppresses apoptosis, and increases metastasis 4. HS3ST1 also promotes non-small cell lung cancer progression through the SPOP/FADD/NF-κB pathway 6. Genetic variants in HS3ST1 associate with coronary artery disease severity, with reduced expression correlating with increased atherosclerotic events 3. These findings establish HS3ST1 as a critical regulator of inflammation and vascular homeostasis with complex, tissue-specific roles in cancer progression.