Ganglioside-induced differentiation-associated protein 2 (GDAP2)

Ganglioside-induced differentiation-associated protein 2 (GDAP2) is a macro domain– and CRAL-TRIO domain–containing protein encoded by the GDAP2 gene, localized to the lysosomal membrane and primarily expressed in the brain[2][3][4][7]. Loss-of-function mutations in GDAP2 are linked to autosomal recessive spinocerebellar ataxia 27 (ARCA27/SCAR27), a neurodegenerative disorder characterized by progressive ataxia, spasticity, and dementia, with widespread neuronal degeneration[3][4][6]. GDAP2 is thought to serve as a dosage-sensitive regulator of neuronal structure, synaptic transmission, and stress responses[4][6]. While the precise biochemical mechanisms remain unresolved, GDAP2’s macro domain is structurally similar to MacroD1/MacroD2 and is implicated in sensing cellular metabolic state, redox balance, and stress pathways; its CRAL-TRIO domain suggests additional roles in lipid binding or transport[2]. Functional studies suggest that GDAP2 mediates neuronal resilience to cellular stress, and both loss and overexpression disrupt neuronal homeostasis, making tight regulation of GDAP2 expression critical for normal neuronal function and survival[4][6]. No known drugs directly target GDAP2 as of this date, and the protein is not currently considered a druggable therapeutic target[3][4][5].

Other names

MACROD3FLJ20142dJ776P7.1SCAR27ATX-GDAP2