TPST1 (tyrosylprotein sulfotransferase 1) catalyzes post-translational O-sulfation of tyrosine residues within acidic protein motifs using 3'-phosphoadenylyl sulfate (PAPS) as a cosubstrate 1. The enzyme localizes to the trans-Golgi compartment through its transmembrane domain, which also facilitates homodimer/oligomer formation necessary for catalytic activity 2. TPST1 processes predominantly secreted proteins, with tyrosine-O-sulfated proteins detected across multiple tissue types including the retina 3. Tyrosine sulfation modulates protein-protein interactions and receptor-ligand binding in inflammation, hemostasis, immunity, and viral entry 1. Disease relevance has emerged from bioinformatics analyses identifying TPST1 as a hub gene in several conditions: it was recognized among six immune-related genes diagnostic for atherosclerosis with concurrent rheumatoid arthritis 4, identified as a key gene in chr7 active Epstein-Barr virus infection with positive correlation to myeloid cell enrichment and persistent EBV infection pathways 5, included in a prognostic signature for bladder cancer immunotherapy response 6, and identified as a potential biomarker in gestational diabetes mellitus 7. However, TPST1 was excluded as the causative gene for Shwachman-Diamond syndrome despite mapping to the disease locus 8.