DNAJC6 encodes auxilin, a heat shock protein family member (Hsp40) co-chaperone that functions as a critical regulator of clathrin-mediated endocytosis and synaptic vesicle recycling. At the molecular level, DNAJC6 recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes ATP-dependent dissociation of clathrin cages through a cyclical mechanism involving multiple rounds of HSPA8 recruitment and ATP hydrolysis 1. This process is essential for synaptic vesicle uncoating and recycling at the presynaptic terminal. DNAJC6 also participates in early clathrin-coated vesicle formation through interaction with dynamin 1 (DNM1). Biallelic loss-of-function mutations in DNAJC6 cause early-onset monogenic Parkinson's disease (PD-19A, PD-19B), characterizing a complex neurodegenerative disorder distinct from typical parkinsonism 2. Affected individuals present with rapidly progressive parkinsonism-dystonia in childhood alongside neurodevelopmental deficits and neuropsychiatric features 3. Patient-derived induced pluripotent stem cell models reveal that DNAJC6 deficiency impairs synaptic vesicle recycling, causes dopaminergic neuron degeneration, induces pathologic α-synuclein aggregation, and disrupts midbrain patterning through impaired WNT-LMX1A signaling 4. DNAJC6 mutations also associate with mitochondrial and lysosomal dysfunctions 4. Currently, no disease-modifying treatments exist, though lentiviral gene transfer restores auxilin expression and rescues clathrin-mediated endocytosis in patient-derived neuronal cultures, suggesting feasibility of gene therapy approaches 3.