DnaJ heat shock protein family member C6 (DNAJC6)

DnaJ heat shock protein family member C6 (DNAJC6), also known as auxilin, is a neuron-specific co-chaperone and member of the DNAJ/HSP40 protein family. It plays an essential role in clathrin-mediated endocytosis at synapses by recruiting Hsp70/HSPA8 to clathrin-coated vesicles and stimulating its ATPase activity, which uncoats vesicles and allows for synaptic vesicle recycling. Mutations in DNAJC6 lead to a rare, severe, juvenile or early-onset form of Parkinson’s disease, often with additional neurodevelopmental and neuropsychiatric symptoms. Disease mechanisms center on impaired clathrin uncoating and synaptic dysfunction, with loss-of-function mutations demonstrating a clear genotype-phenotype link. While no therapies directly target DNAJC6 itself, gene therapy approaches are in experimental development, and levodopa has limited, often problematic efficacy in affected patients[1][2][3][4][5][6][7]. Notes on classification: - While sometimes referred to as a "putative tyrosine-protein phosphatase", the phosphatase domain is predicted to be *catalytically inactive*, so the main established functions are as a co-chaperone and clathrin uncoating factor rather than as an active enzyme[3]. - Molecular classification as a "chaperone accessory factor/co-chaperone" is most accurate according to protein function[1][6].

Other names

AuxilinKIAA0473PARK19DnaJ homolog subfamily C member 6DJC6putative tyrosine-protein phosphatase auxilin

For levodopa: dopamine precursor to address Parkinsonism resulting from defective synaptic vesicle recycling due to DNAJC6 loss of function. Gene therapy: lentiviral-mediated DNAJC6 supplementation shown preclinically to restore auxilin protein and function in iPSC-derived neuronal models.