DNAJC6 Parkinson’s disease: Endolysosomal dysfunction and emerging roles for oligodendrocytes

DNAJC6 encodes auxilin, which is predominantly expressed in neurons and oligodendrocytes. It is involved in clathrin uncoating following clathrin-mediated endocytosis (CME), and loss-of-function genetic variants have been linked to juvenile- and early-onset forms of Parkinson’s disease (PD). Here, we review the genetics and function of the DNAJC6 gene and discuss potential roles it may play in PD. Mechanistic studies across cellular and animal models demonstrate that loss of auxilin impairs synaptic vesicle endocytosis, disrupts endolysosomal trafficking and autophagy, alters lipid homeostasis, and leads to dopaminergic neuron degeneration, while emerging glial data hint at oligodendrocyte contributions to disease pathogenesis.