DnaJ heat shock protein family member C5 (DNAJC5)

DnaJ heat shock protein family member C5 (DNAJC5) is a neuronally enriched co-chaperone (part of the Hsp40 family), best known as cysteine-string protein alpha (CSPα), essential for synaptic function and protein homeostasis. It is primarily located on synaptic vesicles in neurons, where it helps maintain neurotransmission by refolding or stabilizing key synaptic proteins and preventing protein aggregation. DNAJC5 interacts closely with Hsp70 heat shock proteins, regulating their ATPase activity and supporting protein recycling following neurological stimulation. Pathogenic mutations in DNAJC5 cause adult-onset neuronal ceroid lipofuscinosis type 4 (CLN4), characterized by neurodegeneration due to failed synaptic protein quality control; it has also been implicated in broader neurodegenerative processes, including Huntington’s disease. DNAJC5 does not act as a conventional drug target (such as receptor, enzyme, or transporter), but is an important molecular chaperone for synaptic maintenance and may serve as a disease biomarker in research, especially for synaptic dysfunction and genetic forms of neurodegeneration.

Other names

Cysteine-string protein alpha (CSPα)Cysteine string protein (CSP)Ceroid-lipofuscinosis neuronal protein 4CLN4DNAJC5AFLJ00118FLJ13070NCL

Chaperone/co-chaperone facilitating refolding of denatured proteins; Regulates exocytosis by stabilizing synaptic proteins