Homologous to the E6-AP carboxyl terminus (HECT) domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1 (HACE1) is involved in cardioprotection and resistance to oxidative stress, and been proved to be frequently downregulated or mutated in different types of cancer, implying that it may function as a putative tumor suppressor.5–8 As supported, Hace1−/− mice spontaneously develop different tumors.4 Further in vitro and in vivo studies have shown that Hace1 inhibits cell cycle progression of different cancer cells by decreasing the expression of cyclin D1.6,9. The gene discussed is CCND1; the disease is cancer.