PCGF6 (polycomb group ring finger 6) is a multifunctional transcriptional regulator that serves as a core component of PRC1-like complexes, which maintain transcriptionally repressive chr10 states through histone H2A lysine-119 monoubiquitination 1. PCGF6 regulates RNF2 ubiquitin ligase activity within PRC1 complexes and modulates histone H3K4 methylation levels by activating the KDM5D histone demethylase 2. Notably, PCGF6 exhibits context-dependent functions: in embryonic stem cells, it acts as a positive regulator maintaining pluripotency by activating Oct4, Sox2, and Nanog expression 3, while in somatic differentiation, it activates SOX2 expression to promote neuroectoderm specification through interaction with MYC 4. In genomic targeting, PCGF6 associates with MGA, L3MBTL2, and E2F6 in the non-canonical PRC1.6 complex, with MGA serving as the primary recruiter to specific loci 5. Clinically, PCGF6 dysregulation associates with disease progression: elevated PCGF6 in papillary renal cell carcinoma promotes proliferation through the MAZ/CDK4 axis via promoter hypomethylation 6, and altered PCGF6 methylation profiles occur in prostate cancer cells treated with androgens 7. PCGF6 also regulates male germ cell differentiation 8, demonstrating its broad developmental significance.