B4GALT1 encodes beta-1,4-galactosyltransferase 1, a membrane-bound glycoprotein that catalyzes the transfer of galactose to acceptor sugars, functioning primarily in N-linked glycosylation and glycan remodeling 1. The enzyme operates in the Golgi apparatus and can exist in secreted forms involved in extracellular glycan modification 2. Mechanistically, B4GALT1 mediates protein glycosylation with pleiotropic effects. In lung adenocarcinoma, it directly catalyzes N-linked glycosylation of PD-L1, preventing its degradation and promoting immune evasion, while simultaneously stabilizing TAZ protein to activate CD274 transcriptionally 2. In leukemia, B4GALT1 silencing inhibits hedgehog signaling and reverses multidrug resistance 1. In endometrial cancer, the NOLC1-B4GALT1 axis induces O-glycosylation alterations that enhance paclitaxel resistance 3. B4GALT1 demonstrates consistent oncogenic roles across multiple cancer types. Knockdown inhibits glioblastoma proliferation through increased apoptosis and autophagy, reducing lactic acid production and enhancing anti-tumor immune responses 45. Conversely, in colorectal cancer, B4GALT1-dependent galectin-8 N-glycosylation suppresses TGF-β signaling and metastasis 6, suggesting context-dependent functions. Genetically, mutations in B4GALT1 associate with congenital disorders of glycosylation and lipid metabolism abnormalities. These findings position B4GALT1 as a promising therapeutic target for cancer immunotherapy and chemoresistance reversal.