Although EZH2 demonstrates a remarkable level of substrate specificity in catalyzing methylation of only one lysine (H3K27) among all histone peptide substrates, various in vitro and cell-based studies indicate that EZH2 has additional substrates such as JARID2, H2BK120, talin, and transcription factors such as STAT3, which may or may not be desirable targets for cancer (246,271–274). Here, EZH2 is linked to cancer.