DNAJA4 (DnaJ heat shock protein family member A4) is a molecular chaperone belonging to the Hsp40 family that plays diverse roles in cellular stress responses, protein quality control, and disease pathogenesis. As a heat shock protein, DNAJA4 responds to hyperthermia and regulates downstream protective pathways in keratinocytes, including modulation of Clusterin and ERK signaling that protect against hyperthermia-induced cellular injury 1. The protein functions through protein-protein interactions and ubiquitin-proteasome pathways, as demonstrated by its ability to facilitate MYH9 protein degradation via recruitment of PSMD2, thereby suppressing epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma 2. DNAJA4 also regulates cytoskeletal dynamics by modulating F-actin expression through RhoA/ROCK1 pathways in response to hyperthermia 3. The gene is subject to epigenetic regulation through DNA methylation, with hypermethylation observed in various cancers 24. Clinically, DNAJA4 expression levels correlate with disease prognosis and longevity outcomes, with lower expression associated with poor prognosis in nasopharyngeal carcinoma patients and potential involvement in aging processes 25. Additionally, DNAJA4 plays roles in viral replication and antiviral responses 67.