DNAJC5 (cysteine string protein α) is a heat shock protein co-chaperone with dual roles in neuronal protein homeostasis. Primary function: DNAJC5 acts as a co-chaperone for SNAP-25 and other synaptic proteins, facilitating regulated exocytosis and calcium-dependent neurotransmitter release 1. Mechanism: The protein operates through two functionally coupled chaperoning activities—endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, while perinuclear DNAJC5 mediates misfolding-associated protein secretion (MAPS) via interaction with SLC3A2 2. In pathological contexts, DNAJC5 undergoes palmitoylation to form membrane-anchored oligomers that facilitate unconventional α-synuclein secretion 3. Disease relevance: DNAJC5 mutations cause adult neuronal ceroid lipofuscinosis (Kufs disease/CLN4), an autosomal dominant neurodegenerative disorder characterized by lipofuscin accumulation, age-dependent neurodegeneration, and motor deficits 4. Mutations impair normal protein triaging, uncoupling MAPS from microautophagy 2. DNAJC5 dysfunction also associates with parkinsonism through effects on synaptic trafficking 5. Clinical significance: The ubiquitin ligase CHIP-mediated microautophagy represents a potential therapeutic target for restoring lysosomal protection 6, while resveratrol shows neuroprotective promise in disease models 7.