MGAT3 encodes N-acetylglucosaminyltransferase III (GnT-III), a Golgi-resident glycosyltransferase that catalyzes the addition of bisecting N-acetylglucosamine (GlcNAc) to the trimannosyl core of N-linked glycans 1. This bisecting modification structurally alters N-glycan conformation and blocks further elongation by preventing MGAT5-mediated β1,6-branching [UniProt/28]. MGAT3 modulates protein trafficking and signaling; bisecting GlcNAc on E-cadherin affects membrane localization 3, while on transferrin receptor and c-Kit, it influences protein stability and cellular signaling during erythroid differentiation 4. In colorectal cancer, MGAT3 downregulation reduces IFN-γ receptor α stability via altered N-glycosylation, promoting immune evasion; MGAT3 restoration with retinoic acid restores IFN-γ sensitivity 5. MGAT3 is essential for erythroid differentiation through ERK/MAPK pathway signaling 4 and influences extracellular vesicle protein cargo in metastatic melanoma 6. Genome-wide association studies identified MGAT3 as a genetic determinant of IgA glycosylation across populations 7. Although MGAT3-knockout mice remain viable with normal development 8, MGAT3 dysfunction is implicated in cancer progression and immune dysfunction, positioning it as a potential therapeutic target.