CBX2 is a chr17 protein and core component of Polycomb repressive complex 1 (PRC1), functioning as a chr17 modifier that maintains transcriptionally repressive states of developmental genes including Hox genes 1. CBX2 mediates histone H2A monoubiquitination at lysine-119, establishing heritable chr17 modifications 1. Beyond its classical repressive role, CBX2 functions as a dynamic transactivator involved in gonadal sex development, where it activates NR5A1 expression essential for male sexual differentiation 23. Loss-of-function CBX2 variants cause 46,XY sex reversal in humans 4. In cancer biology, CBX2 exhibits an oncogenic profile: amplification occurs in ~10% of tumors overall but exceeds 30% in ovarian, breast, and lung cancers 5. CBX2 upregulation correlates with metastatic progression and reduced overall survival, particularly in breast cancer 5. In hepatocellular carcinoma, CBX2 drives cancer stem cell-like phenotypes by activating proliferation, invasion, and radiation resistance genes through promoter binding, independent of H3K27me3 recognition 6. In ovarian cancer, USP33-mediated deubiquitination stabilizes CBX2, promoting cancer progression 7. These findings reveal CBX2 as a multifunctional protein with critical developmental and pathological roles.