B3GNT2 is a Golgi-resident glycosyltransferase that catalyzes the synthesis of poly-N-acetyllactosamine chains through beta-1,3-N-acetylglucosamine transfer 1. As the major poly-N-acetyllactosamine synthase, B3GNT2 preferentially modifies galactose-based acceptors and represents the predominant enzyme for polylactosamine chain initiation and elongation 21. Mechanistically, B3GNT2 modifies N-glycans on signaling receptors including LRP6, promoting their trafficking and enhancing Wnt/β-catenin signaling 3. B3GNT2 also targets >10 immune ligands and receptors, disrupting tumor-T cell interactions and reducing T cell activation, thereby conferring cancer resistance to immunotherapy 4. Additionally, B3GNT2 regulates the release of coagulation factors FVIII and von Willebrand factor from endothelial cells 5. Genetically, B3GNT2 variants (rs10865331, rs6545925, rs467250) are associated with ankylosing spondylitis (AS) susceptibility and severity in both Chinese and Taiwanese populations 67. Functional genomics indicate B3GNT2 operates in natural killer cells, a key cell type in AS pathogenesis 8. Lower B3GNT2 expression correlates with increased inflammatory markers (ESR, CRP) and disease activity in AS patients 7. These findings position B3GNT2 as an important immunoregulatory glycosyltransferase with clinical relevance to autoimmunity and cancer immunotherapy resistance.