DnaJ homolog subfamily C member 5

DNAJC5 (DnaJ homolog subfamily C member 5) is a 198-amino-acid co-chaperone protein that functions in regulated exocytosis and synaptic transmission (UniProt: Q9H3Z4). It acts as a co-chaperone for the SNARE protein SNAP-25 and is involved in calcium-dependent neurotransmitter release at presynaptic terminals, suggesting a critical role in neuronal signaling. The protein is also implicated in Ceroid lipofuscinosis, neuronal, 4B (CLN4B), an autosomal dominant adult-onset lysosomal storage disease characterized by seizures, dementia, and neurodegeneration.

In Alzheimer's disease, DNAJC5 expression is significantly reduced in human post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of −0.331 across subcellular fractions in TMT-labeled mass spectrometry data, indicating consistent downregulation in the AD brain. This reduction in a protein essential for presynaptic function and neurotransmitter release may contribute to synaptic dysfunction and cognitive decline observed in Alzheimer's pathology.