RNF2 (RING finger protein 2) is an E3 ubiquitin ligase that serves as an essential component of Polycomb repressive complex 1 (PRC1), primarily functioning to monoubiquitinate histone H2A at lysine 119 (H2AK119ub) for epigenetic transcriptional repression 1. The protein employs a read-write mechanism where it recognizes existing H2AK119ub marks through RYBP and positions its RING domains to ubiquitinate unmodified nucleosomes, creating a positive-feedback loop that maintains repressive chr1 domains during DNA replication 1. Beyond its canonical role, RNF2 exhibits diverse regulatory functions including negative regulation of antiviral immunity by promoting TBK1 ubiquitination and degradation 2, modulation of lipid metabolism in alcohol-associated liver disease through USP7 interaction and PI3K/AKT signaling 3, and promotion of hepatocellular carcinoma progression by inducing myeloid-derived suppressor cell chemotaxis via TRAF2-NF-κB signaling 4. RNF2 is subject to post-translational regulation, being stabilized by USP43-mediated deubiquitination at Lys239 and Lys249 2 and promoting degradation of substrates like SBDS through ubiquitination 5. Clinically, RNF2 overexpression correlates with poor prognosis across multiple cancers and represents a potential therapeutic target 6.