DNAJB2 is a co-chaperone that regulates HSP70 family proteins, functioning in both protein folding and degradation pathways 1. As a member of the HSP40/DNAJ family, DNAJB2 activates HSP70 ATPase activity and facilitates substrate binding while simultaneously contributing to ubiquitin-dependent proteasomal degradation of misfolded proteins 1. The protein demonstrates dual localization, with cytoplasmic forms involved in general protein quality control and endoplasmic reticulum-localized isoforms specifically participating in ER-associated degradation 2. DNAJB2 expression occurs at neuromuscular junctions in normal skeletal muscle and increases during muscle regeneration and in protein aggregate myopathies 2. Mutations in DNAJB2 cause autosomal recessive distal hereditary motor neuropathy type 5, characterized by progressive distal motor weakness, often with hearing loss and sometimes parkinsonism 34. The disease mechanism involves loss of DNAJB2 function, leading to toxic protein accumulation including TDP-43 and phospho-alpha-synuclein deposits 3. DNAJB2 deficiency represents a chaperonopathy where impaired protein quality control specifically affects motor neurons, making it one of several chaperone genes associated with hereditary motor neuropathies 45.