RUNX3 is a transcription factor that forms a heterodimeric core-binding factor (CBF) complex with CBFB to regulate gene expression by recognizing specific DNA sequences (5'-TGTGGT-3') in target promoters and enhancers. RUNX3 plays critical roles in immune cell differentiation and tissue homeostasis. In CD8+ T cells, RUNX3 is essential for tissue-resident memory (TRM) cell development and homeostasis, supporting expression of tissue-residency genes while suppressing genes associated with tissue egress 1. RUNX3 activity, often in conjunction with RUNX2, promotes differentiation of cytotoxic CD8+CD103+CD49a+ TRM cells with enhanced immunosurveillance capacity 2. Beyond immunity, RUNX3 functions as a gatekeeping regulator in liver sinusoidal endothelial cells; its deficiency leads to IL-6/JAK/STAT3 pathway activation, LRG1 secretion, and subsequent liver fibrosis progression 3. In fallopian tube epithelium, RUNX3 marks an intermediate state during secretory-to-ciliated cell differentiation 4. Regarding cancer, RUNX3 exhibits context-dependent roles. While traditionally considered a tumor suppressor, recent evidence suggests RUNX3 acts as a "conditional" oncogene, with its oncogenic activity dependent on p53 status 5. In esophageal squamous cell carcinoma, low RUNX3 expression correlates with tumor progression and poor outcomes, suggesting tumor-suppressive functions 6. RUNX3 expression is also regulated by HDAC9-mediated deacetylation, affecting intervertebral disc homeostasis 7.