HS3ST3B1 encodes a heparan sulfate 3-O-sulfotransferase that catalyzes the transfer of sulfate groups to glucosamine residues in heparan sulfate chains, utilizing 3'-phospho-5'-adenylyl sulfate (PAPS) as a sulfate donor. This enzyme specifically modifies IdoUA2S-GlcNS and IdoUA2S-GlcNH2 substrates, creating unique binding sites for viral pathogens including Herpes simplex virus-1. The enzyme plays complex roles in viral pathogenesis, demonstrating both pro- and anti-viral activities depending on the pathogen. HS3ST3B1 exhibits anti-viral effects against hepatitis B virus by inhibiting viral replication and reducing HBV RNA levels through mechanisms independent of direct promoter interaction 12. Conversely, genetic variants in HS3ST3B1 are associated with Plasmodium falciparum parasitaemia susceptibility, with specific SNPs affecting enzyme activity and promoter function 34. In cancer biology, HS3ST3B1 promotes angiogenesis and proliferation in acute myeloid leukemia by inducing VEGF expression and facilitating its shedding from cell surfaces, subsequently activating ERK and AKT signaling pathways 5. The enzyme has also been identified as a potential biomarker in multiple cancer types through genome-wide association studies 678.