IER3 (immediate early response 3) is a stress-responsive gene with complex roles in cellular survival and inflammation. Mechanistically, IER3 inhibits ERK dephosphorylation by phosphatase PP2A, acting as an ERK downstream effector that promotes cell survival 1. The gene is induced by diverse stimuli including growth factors, cytokines, ionizing radiation, and cellular stress, and interferes with NF-κB, MAPK/ERK, and PI3K/Akt signaling pathways 1. In osteogenic differentiation, IER3 functions through BST2 and ERK1/2 pathway activation 2. Disease relevance is substantial. IER3 expression is upregulated in proximal tubules during ischemic acute kidney injury as a pro-apoptotic gene 3, and is elevated in infiltrated macrophages in ischemia-reperfusion-induced AKI, associated with inflammatory responses 4. In gastric cancer, IER3+ myeloid-derived suppressor cells correlate with poor prognosis and treatment resistance 5. Conversely, IER3 is significantly downregulated in type 2 diabetes patients (AUC=0.723) and correlates with immune cell infiltration patterns 6. IER3 is also identified as a prognostic biomarker in idiopathic pulmonary fibrosis 7. Clinically, IER3 represents a promising biomarker for disease stratification and prognosis across multiple conditions, with potential as a therapeutic target in cancer immunotherapy, inflammatory diseases, and regenerative medicine.