XYLT2 (xylosyltransferase 2) catalyzes the first step in glycosaminoglycan proteoglycan biosynthesis by transferring D-xylose from UDP-D-xylose to specific serine residues of core proteins, initiating the assembly of chondroitin sulfate, heparan sulfate, and dermatan sulfate proteoglycans 1. This enzyme functions in the Golgi apparatus and requires magnesium and manganese ion cofactors [GO annotations]. XYLT2 plays critical roles in multiple physiological processes: it regulates heparan sulfate-mediated viral internalization during influenza A virus infection 2, maintains organ homeostasis through proteoglycan biosynthesis 3, and modifies sulfated glycosaminoglycans that serve as host cell targets for fungal pathogens 4. Loss-of-function mutations in XYLT2 cause spondyloocular syndrome (SOS), an autosomal-recessive disorder characterized by spinal compression fractures, osteoporosis, cataracts, and hearing loss 1, 5. XYLT2 is also classified as a congenital disorder of glycosylation (CDG) gene 6, 7, and recent multi-omics analysis identified XYLT2 as a druggable therapeutic target for sporadic Creutzfeldt-Jakob disease 8. The enzyme's systemic importance is underscored by evidence that XYLT2 knockout mice exhibit widespread organ dysfunction including splenomegaly and altered pulmonary responses 3.