What question did this study set out to answer?

The research aims to explore the genetic and functional implications of DNAJC6 in Parkinson’s disease, focusing on auxilin's roles.

April 6, 2026npj Parkinson s Disease0 citationsOpen Access

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

AAAngel G AllenThe University of Adelaide SSSarah J. StednitzThe University of Melbourne MLMichael LardelliThe University of Adelaide

Key Points

The research aims to explore the genetic and functional implications of DNAJC6 in Parkinson’s disease, focusing on auxilin's roles.
Review literature on DNAJC6 genetics and function
Analyze cellular and animal models regarding auxilin loss
Examine impacts on synaptic vesicle endocytosis and endolysosomal trafficking
Assess lipid homeostasis and dopaminergic neuron health
Loss of auxilin leads to impaired synaptic vesicle endocytosis
Disruption of endolysosomal trafficking and autophagy observed
Altered lipid homeostasis linked to neuron degeneration
Emerging data suggests oligodendrocytes are involved in disease mechanisms

Abstract

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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