The GM2-activator protein (GM2AP) is an essential cofactor for the lyso-somal degradation of ganglioside GM2 by b-hexosaminidase A (HexA). It mediates the interaction between the water-soluble exohydrolase and its membrane-embedded glycolipid substrate at the lipid–water interface. Functional deficiencies in this protein result in a fatal neurological storage disorder, the AB variant of GM2 gangliosidosis.