DNAJC7 is a co-chaperone that regulates molecular chaperones HSP70 and HSP90 in protein folding, particularly for steroid receptors and disease-associated proteins 1. The protein contains both a J-domain for HSP70 interaction and tetratricopeptide repeat (TPR) domains for HSP90 binding, connecting these two major chaperone systems 1. DNAJC7 specifically binds natively folded structural elements in tau protein through its TPR domain, recognizing a β-turn containing the amyloid motif, thereby preventing tau aggregation and amyloid formation 2. The protein also regulates TDP-43 condensate dynamics, promoting disassembly of stress-induced TDP-43 aggregates 3. DNAJC7 mediates neuroprotection by modulating HSF1 stress response pathways and maintaining protein homeostasis in motor neurons 4. Disease relevance is significant, as pathogenic variants in DNAJC7 cause familial and sporadic amyotrophic lateral sclerosis (ALS) through loss-of-function mechanisms 13. Both heterozygous and biallelic mutations lead to ALS with TDP-43 pathology, motor neuron degeneration, and impaired stress responses 43. DNAJC7's protective effects depend on its J-domain's ability to stimulate HSP70 ATPase activity, and disease-associated mutations abolish this protective function 5.