MGAT1 (alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase) is a Golgi-localized glycosyltransferase that catalyzes the initial step in converting high-mannose to complex and hybrid N-linked glycans 1. The enzyme transfers N-acetylglucosamine to mannose-containing oligosaccharides, a process essential for proper protein glycosylation 2. Mechanistically, MGAT1 regulates cell-surface protein expression and trafficking. In immune cells, MGAT1-mediated N-glycosylation of CD73 enables its dimerization and membrane translocation via VAMP3, suppressing CD8+ T cell function 3. In regulatory T cells, lactate-induced upregulation of mitochondrial MGAT1 promotes N-glycosylation of progranulin and HYOU1, enhancing oxidative phosphorylation and Treg immunosuppressive capacity 4. Clinically, MGAT1 shows context-dependent roles in disease. In triple-negative breast cancer, MGAT1 overexpression promotes immune evasion; blocking MGAT1 glycosylation activity with W-GTF01 restores anti-PD-L1 therapy responsiveness 3. Conversely, in pancreatic ductal adenocarcinoma, high MGAT1 expression correlates with improved prognosis and reduced cell proliferation 5. MGAT1 was identified as a causal factor in atherosclerosis through proteogenomic analysis 6. MGAT1 expression is regulated by Wnt/β-catenin signaling in hepatocellular carcinoma, promoting tumor growth 7.