DnaJ homolog subfamily C member 5, also known as cysteine string protein or CSP is a protein, that in humans encoded by the DNAJC5 gene. It was first described in 1990. Gene In humans, the gene is located on the long arm of chromosome 20 (20q13.33) on the Watson (positive strand). The gene is 40,867 bases in length and the encoded protein has 198 amino acids with a predicted molecular weight of 22.149 kiloDaltons (kDa). The weight of the mature protein is 34kDa. This gene is highly conserved and found both in invertebrates and vertebrates. In humans, a pseudogene of this gene is located on the short arm of chromosome 8. Structure The organisation of the protein is as follows: an N-terminus phosphorylation site for protein kinase A a J domain (~70 amino acids) a linker region a cysteine motif consisting of 13–15 cysteines within a stretch of 25 amino acids. It is heavily palmitoylated in the cysteine string motif. a less conserved C-terminal domain Tissue distribution This protein is abundant in neural tissue and displays a characteristic localization to synaptic and clathrin coated vesicles. It is also found on secretory vesicles in endocrine, neuroendocrine and exocrine cells. This protein makes up ~1% of the protein content of the synaptic vesicles. DNAJC5 appears to have a role in stimulated exocytosis. Function The encoded protein is a member of the J protein family. These proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins (Hsp70). DNAJC5 is a guanine nucleotide exchange factor for Gα proteins. CSPα plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. It is known to play a role in cystic fibrosis and Huntington's disease. This protein has been proposed as a key element of the synaptic molecular machinery devoted to the rescue of synaptic proteins that have been unfolded by activity dependent stress. Syntaxin 1A, a plasma membrane SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for neurotransmission, forms a complex with CSPα, a G protein and an N-type calcium channel. Huntingtin may be able displace both syntaxin 1A and CSPα from N-type channels. CSP interacts with the calcium sensor protein synaptotagmin 9 via its linker domain. Huntingtin-interacting protein 14, a palmitoyl transferase, is required for exocytosis and targeting of CSP to synaptic vesicles. The palmitoyl residues are transferred to the cysteine