POMT1 (protein O-mannosyltransferase 1) catalyzes the transfer of mannosyl residues to serine and threonine hydroxyl groups on proteins, functioning as a key enzyme in the O-mannosylation pathway. This enzymatic activity requires heterodimeric complex formation with POMT2; neither protein exhibits catalytic activity alone 1. POMT1 is essentially dedicated to O-mannosylation of alpha-dystroglycan (α-DG), a critical component of the dystrophin-glycoprotein complex that anchors muscle fibers to the extracellular matrix at the basement membrane 2. Mutations in POMT1 cause autosomal recessive muscular dystrophy-dystroglycanopathies (MDDGs), characterized by defective α-DG glycosylation 1. Clinical manifestations span a broad phenotypic spectrum including congenital muscular dystrophy with brain and eye anomalies (Walker-Warburg syndrome) or later-onset limb-girdle muscular dystrophy, frequently accompanied by intellectual disability and neurological abnormalities 3. In a large Chinese dystroglycanopathy cohort, POMT1 mutations (16 patients) were associated with mental retardation as a distinguishing clinical feature 4. POMT1 is expressed prominently in astrocytes and neurons, suggesting roles in basement membrane formation and neuronal migration during CNS development 2. Over 76 disease-associated POMT1 mutations have been reported, enabling molecular diagnosis and genetic counseling for affected families 1.