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

Apr 4, 2026NPJ Parkinson's disease

Parkinson's Disease Linked to DNAJC6 Gene: Problems in Cellular Waste Processing and New Roles for Brain Support Cells

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Loss of auxilin, encoded by DNAJC6, could lead to dopaminergic neuron degeneration and is associated with juvenile- and early-onset Parkinson's disease.

DNAJC6 is predominantly expressed in neurons and oligodendrocytes.
Loss-of-function genetic variants in DNAJC6 have been linked to Parkinson's disease.
Impaired synaptic vesicle endocytosis occurs when auxilin is lost.
Disruption of endolysosomal trafficking and autophagy may result from auxilin loss.
Altered lipid balance is associated with the absence of auxilin.
Emerging data suggest that oligodendrocytes may contribute to the pathogenesis of Parkinson's disease.

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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.

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

Abstract

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