Sacsin molecular chaperone (SACS)

Sacsin molecular chaperone (SACS) is a large, multidomain protein highly expressed in neurons—especially Purkinje cells in the cerebellum—and present in skin and muscle[1][2][3][4]. Structurally, sacsin contains a ubiquitin-like (UbL) domain at the N-terminus, a J-domain homologous to Hsp40 co-chaperones, regions with Hsp90-like ATPase folds, and a C-terminal HEPN domain capable of nucleotide binding[1][2]. Sacsin acts as a co-chaperone, integrating Hsp70 chaperone function and ubiquitin-proteasome degradation, and is essential for protein homeostasis, cytoskeletal integrity, and mitochondrial network organization[1][2][4]. Loss or mutation of sacsin causes ARSACS, a severe neurodegenerative disorder characterized by early-onset spastic ataxia, peripheral neuropathy, and progressive cerebellar dysfunction, due to abnormal cytoskeletal aggregation (notably neurofilament bundling) and possible mitochondrial dysfunction[3][4]. No small molecule therapeutics or interventions targeting SACS are currently known.

Other names

SacsinDNAJC29KIAA0730ARSACSDKFZp686B15167SPAX6PPP1R138DnaJ homolog subfamily C member 29protein phosphatase 1 regulatory subunit 138spastic ataxia of Charlevoix-Saguenay protein