PCGF2 (polycomb group ring finger 2) is a transcriptional repressor that functions as a core component of Polycomb Repressive Complex 1 (PRC1), which maintains gene silencing through chr17 remodeling and histone modifications 1. The protein regulates histone H2A monoubiquitination at lysine 119 (H2AK119ub1), rendering chr17 transcriptionally repressed 12. PCGF2 controls cell proliferation and differentiation by directly binding to gene promoters and regulating target gene expression, including HOXA7 in granulocytic differentiation 3 and progesterone receptor (Pgr) in ovarian folliculogenesis 2. The protein interacts with UBE2I to negatively regulate sumoylation processes, affecting protein degradation pathways 4. PCGF2 has context-dependent roles in cancer, acting as a tumor suppressor in some contexts while promoting colon cancer progression through CENPE upregulation 5. Disease relevance includes Turnpenny-Fry syndrome, caused by de novo missense mutations affecting the conserved Pro65 residue, resulting in craniofacial, neurological, cardiovascular, and skeletal abnormalities 6. These mutations likely create dominant-negative effects by disrupting histone binding capabilities while sequestering other PRC1 components 6. PCGF2 dysregulation has also been implicated in Alzheimer's disease and acute promyelocytic leukemia 73.