The enhancer of zeste homolog 2 (EZH2) is a critical member of the Polycomb Repressive Complex 2 (PRC2) that regulates histone methylation mainly via lysine 27 at histone H3 (H3K27), a modification associated to transcriptional silencing [97] that is found upregulated in many tumor types. The gene discussed is EZH2; the disease is neoplasm.