B3GAT1 (beta-1,3-glucuronyltransferase 1) is a Golgi membrane-resident glycosyltransferase that catalyzes glucuronic acid addition to protein glycans, particularly those on plasma glycoproteins and the L2/HNK-1 carbohydrate epitope 1. The enzyme requires saturated sphingomyelins for activity and modifies both glycoproteins and glycosaminoglycans. Mechanistically, B3GAT1 prevents cell surface sialic acid expression by modifying glycan structures 2. This activity restricts influenza virus entry, with B3GAT1 overexpression in respiratory epithelium protecting mice from lethal influenza challenge and blocking multiple sialic acid-dependent viruses including enterovirus D68 2. Additionally, B3GAT1 maintains vascular endothelial glycocalyx integrity; pathogenic downregulation via bacterial PPAD-mediated histone H3 citrullination causes endothelial damage 3. B3GAT1 associates with multiple disease states. Genetic variants in B3GAT1 influence plasma N-glycan composition in European populations 1 and show significant association with schizophrenia risk through altered brain glycosylation 45. Lower B3GAT1 expression correlates with insect venom allergy in mastocytosis patients 6, while genetic evidence links B3GAT1 to prostate cancer susceptibility 7. Clinically, B3GAT1 represents a promising host-directed antiviral therapeutic target with broad-spectrum potential against respiratory viruses, given its well-tolerated respiratory epithelial overexpression and protective efficacy in vivo 2.