POMGNT1 is a Golgi glycosyltransferase that catalyzes the addition of N-acetylglucosamine (GlcNAc) to O-linked mannose residues on glycoproteins, specifically synthesizing the GlcNAc(β1-2)Man(α1-)O-Ser/Thr moiety on α-dystroglycan and other O-mannosylated substrates 1. This enzymatic activity provides the structural foundation for subsequent carbohydrate modifications on glycoproteins 2. POMGNT1 localizes to the Golgi membrane and is expressed particularly in astrocytes and immature neurons, where it functions in basement membrane formation at the glia limitans 3. POMGNT1 mutations cause a spectrum of muscular dystrophy-dystroglycanopathies characterized by deficient α-dystroglycan glycosylation. These include congenital disorders with severe phenotypes affecting both central and peripheral nervous systems 4. In dystroglycanopathy cohorts, POMGNT1 mutations are associated with more severe clinical presentations compared to other causative genes 4. Congenital manifestations include lissencephaly, eye anomalies, and developmental delay 35. Beyond inherited dystrophies, POMGNT1 expression correlates with glioblastoma grade and progression, where elevated levels predict poor prognosis and promote tumor growth through EGFR/β-catenin pathway activation 6. Prenatal diagnostic applications have identified POMGNT1 variants in cases of congenital hydrocephalus 7.