GM2A encodes the ganglioside GM2 activator protein, a non-catalytic lysosomal protein essential for ganglioside catabolism 1. GM2A functions as a lipid binding and transport protein that extracts GM2 ganglioside molecules from neuronal membranes and presents them in soluble form to the lysosomal enzyme β-hexosaminidase A, which cleaves N-acetyl-D-galactosamine to convert GM2 to GM3 1. The protein exhibits cholesterol transfer activity and phospholipase activity, accommodating multiple single-chain phospholipids in its large binding pocket 1. GM2A mutations cause AB-variant GM2 gangliosidosis, a rare autosomal recessive lysosomal storage disorder characterized by severe neurological deterioration beginning in infancy 23. Pathologically, GM2A deficiency results in GM2 and GA2 ganglioside accumulation in neurons, leading to gliosis, demyelination, and neuronal death 45. Recent evidence suggests elevated GM2A in Alzheimer's disease brain tissue reduces neurite integrity and spontaneous neuronal activity, indicating potential involvement in neurodegeneration beyond classical lysosomal storage disease 6. Animal models confirm that GM2A-deficient mice with impaired compensatory NEU3-mediated degradation pathways exhibit severe ataxia, neurological decline, and early lethality, phenotypically resembling human infantile-onset disease 5.