HS3ST1 encodes heparan sulfate-glucosamine 3-O-sulfotransferase 1, a Golgi-resident enzyme that catalyzes the transfer of sulfate to position 3 of glucosamine residues in heparan sulfate (HS) using PAPS as the sulfate donor 123. This modification is the rate-limiting step in HS biosynthesis and is essential for forming the antithrombin-binding pentasaccharide motif that defines anticoagulant heparan sulfate 13. HS3ST1 shows tissue-restricted expression and belongs to a family of related sulfotransferases with overlapping but distinct substrate specificities 45. In disease contexts, HS3ST1 plays context-dependent roles. In pancreatic cancer, antithrombin-binding heparan sulfate synthesized by HS3ST1 is expressed in healthy tissue but lost during malignant progression; HS3ST1 inactivation in pancreatic ductal adenocarcinoma cells increases inflammation and metastatic potential 6. Conversely, HS3ST1 promotes non-small-cell lung cancer progression through the SPOP/FADD/NF-κB pathway 7. In colorectal cancer, HS3ST1 expression in tumor-infiltrating innate lymphoid cells associates with tumorigenesis, and HS3ST1 deficiency suppresses tumor growth 8. Functionally, the HS3ST1 gene product mediates antithrombin's anti-inflammatory activity that protects against atherosclerosis 9, and genetic variants in HS3ST1 associate with severity of coronary artery disease. These findings position HS3ST1 as a multifunctional regulator at the intersection of coagulation, immunity, and tumorigenesis.