DNAJB4 is a co-chaperone protein belonging to the heat shock protein-40 (HSP40) family that plays critical roles in protein homeostasis and disease regulation. As a probable chaperone, DNAJB4 stimulates ATP hydrolysis and facilitates protein folding mediated by HSPA1A/B 1. The protein demonstrates diverse cellular functions, including recognition of structured elements in disease-related prion-like domains such as those found in TDP-43, where it influences phase separation and aggregation processes 2. DNAJB4 expression is regulated by circadian clock proteins, with upregulation leading to mitochondrial calcium overload and neuronal damage in diabetic conditions 3. Clinically, DNAJB4 loss-of-function variants cause congenital myopathy with early respiratory failure and spinal rigidity, with missense variants in the J-domain associated with more severe phenotypes including earlier onset and higher mortality 4. In cancer biology, DNAJB4 functions as a tumor suppressor in breast cancer, where it activates the Hippo signaling pathway to promote cell apoptosis and enhance immune infiltration while inhibiting cell proliferation and migration 56. The protein can also be targeted by HERV-derived microRNAs in bladder cancer, suggesting broader oncological relevance 7.