IER5 is an immediate-early response transcription factor with dual roles in stress response and cell cycle regulation. As a transcriptional regulator, IER5 mediates positive regulation of heat shock protein genes in an HSF1-dependent manner 1, enabling cellular recovery from thermal stress through enhanced protein refolding capacity 1. IER5 also negatively regulates CDC25B expression, linking it to cell cycle checkpoint control 2. Mechanistically, IER5 functions as a PP2A adapter protein that facilitates dephosphorylation of key substrates including HSF1 and MDM2 34. Through MDM2 dephosphorylation, IER5 stabilizes p53, the tumor suppressor protein 4. Nuclear localization via a conserved bipartite NLS is essential for IER5 function 5. IER5 expression is induced by ionizing radiation, heat stress, and proteotoxic agents, positioning it at the intersection of DNA damage response and proteostasis pathways 61. In cancer contexts, IER5 overexpression enhances sensitivity to radiation and cisplatin-induced apoptosis in hepatocellular carcinoma cells 7. Dietary antioxidants can modulate IER5-mediated DNA repair pathways 8, suggesting therapeutic potential in radioprotection strategies.