Ganglioside GM2 activator (GM2A)

Ganglioside GM2 activator (GM2A) is a small, soluble glycolipid transport protein and cofactor essential for the lysosomal enzyme beta-hexosaminidase A to degrade ganglioside GM2 and related glycosphingolipids. GM2A binds GM2 ganglioside, extracts it from lysosomal membranes, and presents it to beta-hexosaminidase A for hydrolysis of the terminal N-acetyl-D-galactosamine, allowing conversion to GM3. Deficiency or mutation of GM2A results in GM2-gangliosidosis (AB variant), a rare autosomal recessive neurodegenerative disorder with clinical features nearly identical to Tay–Sachs and Sandhoff diseases. Besides its central catabolic role in sphingolipid metabolism, GM2A also participates in innate immune functions through lipid presentation to T cells. The protein belongs to the ML domain family, related to innate immunity and lipid metabolism.

Other names

GM2 activatorGM2 ganglioside activatorGM2-APGM2APSAP-3Cerebroside sulfate activator proteinSphingolipid activator protein 3

Facilitates degradation of ganglioside GM2 by presenting it to beta-hexosaminidase A, enabling its hydrolysis