POMT2 encodes protein O-mannosyltransferase 2, a key enzyme catalyzing the first step of O-linked mannosyl glycosylation by transferring mannosyl residues to serine or threonine residues 1. Functional enzyme activity requires heterodimerization with POMT1; expression of either protein alone is insufficient 23. The complex is essentially dedicated to O-mannosylation of alpha-dystroglycan (α-DG) and select other proteins, but not cadherins 3. Localizing to the endoplasmic reticulum, POMT2 is crucial for maintaining proper α-DG glycosylation, which stabilizes the dystrophin-associated glycoprotein complex at the muscle sarcolemma. POMT2 mutations cause alpha-dystroglycanopathies, a group of congenital muscular dystrophies characterized by deficient α-DG glycosylation 4. Disease presentations range from severe Walker-Warburg syndrome—featuring brain and eye anomalies with mortality before age three 5—to milder limb-girdle muscular dystrophy type R14 with adult-onset proximal weakness 6. Clinical manifestations include exercise intolerance, mental retardation, elevated creatine kinase, and myopathic muscle pathology 7. Recent evidence indicates pathogenic POMT2 variants trigger nonsense-mediated mRNA decay and protein structural instability 6. Additionally, POMT2 deficiency may contribute to cardiac complications in carbohydrate metabolism disorders 8, expanding its clinical significance beyond skeletal muscle.