DnaJ heat shock protein family member C13 (DNAJC13)

DnaJ heat shock protein family member C13 (DNAJC13) encodes a large co-chaperone protein primarily localized to endosomes, where it regulates membrane recycling, clathrin-mediated endocytosis, and cargo sorting via interactions with Hsc70, the retromer/SNX1 complex, and components of the actin cytoskeleton. Its conserved J-domain allows binding to Hsp70 chaperones, stimulating ATP hydrolysis required for protein refolding and quality control. DNAJC13 is central to maintaining endosomal membrane dynamics and autophagic flux, crucial for neuronal proteostasis. Pathogenic mutations, such as N855S, disrupt endosomal trafficking and protein recycling, causing α-synuclein accumulation, and are genetically linked to familial Parkinson’s disease and plausibly essential tremor. DNAJC13 is not currently a direct therapeutic target, but its pathogenic role and critical cellular functions make it significant in the context of neurodegenerative disease biology.

Other names

Receptor-mediated endocytosis 8RME-8PARK21KIAA0678DnaJ (Hsp40) homolog, subfamily C, member 13DnaJ domain-containing protein RME-8Required for receptor-mediated endocytosis 8

Not directly targeted by drugs; disease mutations have a toxic gain-of-function affecting endosomal trafficking, α-synuclein metabolism, and autophagy