HS3ST3A1 encodes a sulfotransferase that catalyzes 3-O-sulfation of glucosamine residues on heparan sulfate (HS) chains using 3'-phospho-5'-adenylyl sulfate (PAPS) as a sulfate donor. This modification generates specific HS domains that regulate cell surface binding and signaling. Unlike the related enzyme HS3ST1, HS3ST3A1 does not convert non-anticoagulant to anticoagulant HS. The enzyme facilitates Herpes simplex virus-1 entry by generating HS receptors on infected cells. HS3ST3A1 is enriched in myoepithelial cells and regulates fibroblast growth factor receptor (FGFR) signaling during salivary gland development and homeostasis 1. Genetic variants in HS3ST3A1 associate with Plasmodium falciparum parasitaemia, with the rs28470223 promoter variant reducing transcriptional activity 23. A promoter SNP also associates with white matter hyperintensity volume in elderly individuals without dementia, suggesting involvement in neurodegenerative processes 4. Expression is decreased in pre-eclamptic placental tissue and correlates with neonatal birth weight and maternal blood pressure 5. In multiple myeloma, HS3ST3A1-mediated 3-O-sulfation of syndecan-1 promotes APRIL binding and drug resistance 6. Recent evidence implicates HS3ST3A1 in tau protein phase separation and Alzheimer's disease pathology 7, and genetic variants associated with tooth crown dimensions are partly derived from Neanderthal introgression 8. The gene appears dysregulated in neuromuscular disease contexts 9.