Recent studies have suggested that increased cyclin D1 level due to the dysregulation of its E3 ligase CRL4 leads to the resistance towards CDK4/6is.14–16 Since MG53 overexpression caused significant downregulation of cyclin D1 (Figs. 3a, b and 6a and Supplementary Fig. 7a), we speculated that ectopic expression of MG53 may sensitize cancer cells to palbociclib. The gene discussed is CDK4; the disease is cancer.