B3GALT5 encodes beta-1,3-galactosyltransferase 5, a glycosyltransferase that catalyzes the transfer of galactose to N-acetylglucosamine-based acceptors, particularly in the synthesis of core3 O-linked glycans and glycosphingolipids 1. The enzyme plays critical roles in maintaining intestinal barrier integrity through proper mucin O-glycosylation, where B3GALT5 deficiency impairs mucin2 glycosylation and increases intestinal permeability, leading to metabolic disorders including obesity and insulin resistance 2. B3GALT5 is regulated by IL-22 signaling in intestinal epithelial cells and is essential for mucosal barrier maintenance and tissue regeneration 3. In stem cell biology, B3GALT5 controls the synthesis of pluripotency markers SSEA-3 and SSEA-4, with its knockout facilitating transition to naive pluripotency and altering glycosphingolipid profiles 14. The enzyme also synthesizes cancer-associated glycans including CA19-9 and sialyl Lewis a, which promote pancreatitis and pancreatic cancer through EGFR signaling activation 5. High B3GALT5 expression correlates with poor prognosis in hepatocellular carcinoma and breast cancer, promoting tumor progression, metastasis, and epithelial-to-mesenchymal transition 67. B3GALT5 expression is transcriptionally controlled by HNF1α/β, NFYA, and STAT3 signaling pathways 84.