Since the discovery of Praja ring finger protein 1 (Praja1) in 2011, an E3 ubiquitin ligase that directly ubiquitinates EZH2 to reduce its protein levels and inhibit breast cancer progression, several other E3 ubiquitin ligases have been identified to regulate EZH2 protein stability in tumor cells [47, 48]. This evidence concerns the gene EZH2 and breast cancer.