Since alterations of EZH2 and PRC2, including EZH2 overexpression (Chase and Cross, 2011; Völkel et al., 2015; Zeng et al., 2022), are frequently associated with a wide variety of human cancers, it is likely that the lysine methylation-dependent proteolysis in cancer cells is affected at various levels, including the altered L3MBTL3 protein levels, to prevent EZH2 proteolysis. Here, L3MBTL3 is linked to cancer.