MGAT5 (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase) catalyzes the addition of β1,6-linked N-acetylglucosamine to complex N-glycans, a post-translational modification with critical roles in immunity and cancer. Primary function: MGAT5 adds branched N-glycan structures to proteins, regulating protein-protein interactions and cell signaling 1. Mechanism: MGAT5-mediated β1,6-GlcNAc branching stabilizes growth factor receptors, reduces intercellular adhesion, and promotes cell migration 1. In immune cells, MGAT5 branching promotes CD8+ T-cell exhaustion through increased PD1 and Tim3 expression 2. Disease relevance: MGAT5 expression is elevated in multiple cancers, including lung adenocarcinoma and melanoma, supporting tumor growth and metastasis 34. MGAT5 expression on tumor cells shields them from CAR T cell killing by disrupting immunological synapse formation 5. Genetic variants in MGAT5 associate with severe ulcerative colitis through altered T-cell glycosylation 6. Clinical significance: MGAT5 deletion in CD8+ T cells and CAR T cells enhances anti-tumor immunity in solid tumors and glioblastoma 27. MGAT5 knockout in immunotherapy-resistant pancreatic cancer increases sensitivity to immune checkpoint blockade 8. MGAT5 represents a potential therapeutic target and prognostic biomarker in cancer and autoimmune disease.