Dnajc6 — Dnaj Heat Shock Protein Family Member A6 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
DNAJC6 (DnaJ Heat Shock Protein Family Member A6), also known as auxilin-2, is a neuronal-specific co-chaperone protein that plays an essential role in synaptic vesicle recycling. Located on chromosome 19q13.43, this gene encodes a protein primarily expressed in neurons throughout the brain, with particularly high levels in the substantia nigra, basal ganglia, and cerebral cortex[1].
The protein functions as a specialized co-chaperone within the Hsp40 family, working in concert with Hsc70 to facilitate the disassembly of clathrin coats during synaptic vesicle endocytosis. This process is critical for maintaining the synaptic vesicle pool and ensuring continuous neurotransmitter release at presynaptic terminals. DNAJC6 is distinct from its relative DNAJC5 (cystinosin) in that it is neuron-specific and functions exclusively in the clathrin-mediated endocytic pathway[2].
Recessive loss-of-function mutations in DNAJC6 cause early-onset Parkinsonism, typically manifesting before age 30. The disease is characterized by rapid progression and prominent motor features, though patients often show good response to levodopa therapy. Understanding DNAJC6 function provides insights into how defects in synaptic vesicle recycling lead to selective dopaminergic neuron vulnerability in Parkinson's disease[3].
DNAJC6 encodes the auxilin-2 protein, a neuronal co-chaperone of the Hsp40 family that plays a critical role in synaptic vesicle endocytosis 1(https://pubmed.ncbi.nlm.nih.gov/21325632/). Unlike its close relative DNAJC5 (cystinosin), DNAJC6/Auxilin-2 is specifically expressed in neuronal tissues and regulates clathrin-mediated endocytosis.
Recessive loss-of-function mutations in DNAJC6 cause early-onset Parkinsonism with prominent motor features 3(https://pubmed.ncbi.nlm.nih.gov/23612983/). Key characteristics include:
DNAJC6 mutations are among the genetic causes of juvenile-onset Parkinsonism (<20 years), along with PARK2 (parkin) and PINK1 mutations.
DNAJC6 shows neuron-specific expression:
DNAJC6 loss-of-function leads to:
The study of Dnajc6 — Dnaj Heat Shock Protein Family Member A6 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Last updated: 2026-03-03
Edvardson S, et al. A deleterious mutation in DNAJC6 causes early-onset progressive Parkinson's disease. Mov Disord. 2012;27(2):213-218. DOI:10.1002/mds.24041 ↩︎
Roosen DA, et al. DNAJC6 mutations: Yet another cause of early-onset Parkinson's disease. Brain. 2014;137(Pt 5):e275. DOI:10.1093/brain/awu010 ↩︎
Koroglu C, et al. DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability. Parkinsonism Relat Disord. 2013;19(3):320-324. DOI:10.1016/j.parkreldis.2012.11.006 ↩︎