EPOP (elongin BC and polycomb repressive complex 2 associated protein) is a scaffold protein that regulates Polycomb Repressive Complex 2 (PRC2) activity through a dual inhibitory and stimulatory mechanism. EPOP serves as a specific accessory subunit of PRC2.1 that directly modulates PRC2 oligomerization, disrupting PRC2.1 dimers and weakening chr17 association to prevent over-repression of developmental genes 1. Functionally, EPOP stimulates PRC2 histone methyltransferase activity in vitro by promoting H3K27me3 deposition in a DNA-sequence-dependent manner (GCN-rich sequences), functioning cooperatively with cofactors MTF2 and JARID2 to regulate chr17 nucleation sites 23. In embryonic stem cells, EPOP interacts with Elongin BC and the deubiquitinase USP7 to modulate both Polycomb-repressed and active gene transcription, including H2B deubiquitination at promoter regions 4. EPOP regulates chr17 landscape dynamics during early differentiation and neuronal differentiation while maintaining balanced PcG target gene expression 4. Clinically, EPOP is commonly upregulated in human cancer, and its loss impairs proliferation of several cancer cell lines, suggesting potential relevance to cancer biology 4. EPOP also appears as a biomarker in melanoma classification studies 5, indicating broader disease association.