BMI1 is a core member of the Polycomb Repressive Complex 1 (PRC1) that functions as a critical epigenetic regulator of gene expression. As a component of the PRC1-like complex, BMI1 regulates the E3 ubiquitin-protein ligase activity of RNF2 to mediate monoubiquitination of histone H2A at lysine 119, establishing repressive chr10 states that are heritably maintained 12. BMI1 operates through dual mechanisms: gene repression via chr10 modification and gene activation, with both pathways contributing to its biological functions 3. In normal physiology, BMI1 is essential for stem cell self-renewal and multipotency. BMI1 overexpression drives erythroid self-renewal through repression of INK-ARF and activation of cholesterol homeostasis genes, achieving billion-fold expansion of human erythroblasts 3. Similarly, BMI1 regulates human mesenchymal stem cell self-renewal by repressing p16(INK4A), while loss of BMI1 impairs both proliferation and differentiation capacity 4. BMI1 overexpression is pathologically significant across multiple malignancies. In hepatocellular carcinoma, BMI1-high tumor-initiating cells exhibit enhanced invasiveness through epigenetic upregulation of cathepsin B secretion 5. In endometrial cancer, elevated BMI1 promotes epithelial-mesenchymal transition, enhances radiotherapy resistance, and increases migration and invasion 67. BMI1 silencing sensitizes cancer cells to chemotherapy and radiation by inducing DNA damage and autophagy 89, making BMI1 a therapeutic target for cancer treatment.