EED (Embryonic Ectoderm Development) is a core component of the Polycomb Repressive Complex 2 (PRC2), functioning as an essential epigenetic regulator. As part of the PRC2/EED-EZH2 complex, EED catalyzes histone H3 lysine-27 trimethylation (H3K27me3), a repressive chr11 mark that silences target genes including HOX genes and tumor suppressors 1. EED acts as an allosteric reader of H3K27me3, binding trimethylated histone marks to sustain PRC2 activity while also recognizing H3K27ac marks to facilitate gene activation, revealing unexpected complexity in its regulatory role 2. Mechanistically, EED contains five conserved WD-repeat motifs critical for protein folding and PRC2 complex assembly 3. Clinically, EED dysregulation is implicated in cancer development, as PRC2-mediated H3K27me3 dysregulation occurs across multiple malignancies. Targeting EED through small-molecule inhibitors and protein-protein interaction modulators represents a novel therapeutic strategy, particularly as direct EZH2 inhibition shows limited efficacy in certain cancers 4, 5. Beyond cancer, EED participates in m6A-histone modification crosstalk regulating endometrial receptivity 6, and clinical mutations in EED cause Cohen-Gibson syndrome. Notably, EED also exerts antiviral activity by negatively affecting HIV-1 assembly and release 7.