Maspardin (SPG21)

Maspardin (SPG21) is a ubiquitously expressed, non-enzymatic protein containing an alpha/beta hydrolase fold domain, but unlike most enzymes in this family, maspardin lacks catalytic activity and is chiefly involved in protein–protein interactions[1]. Initially characterized as an intracellular negative modulator of CD4-dependent T cell activation, maspardin also localizes to cytoplasm and intracellular membranes including the trans-Golgi network, endolysosomes, and late endosomal compartments[1][2][4]. The protein interacts directly with CD4 (in T cells), ALDH16A1 (aldehyde dehydrogenase), and RAB7A (a small GTPase regulating lysosomal trafficking)[1][4][5]. Loss-of-function mutations in maspardin cause Mast syndrome (hereditary spastic paraplegia type 21), a neurodegenerative disorder marked by progressive spasticity, cognitive decline, and cerebral white matter changes[1][4]. Although its detailed molecular function remains incompletely understood, recent evidence points to a role in regulating endolysosomal signaling pathways, including mTORC1, and protein sorting or membrane trafficking in neurons[4]. There are no drugs known to target maspardin directly, and it is not currently considered a therapeutic target.

Other names

ACP33BM-019GL010MASTABHD21Acid cluster protein 33Spastic paraplegia 21 proteinSpastic paraplegia 21 autosomal recessive Mast syndrome proteinmaspardinSPG21