The MDM2/MDMX-p53 circuitry plays a pivotal role in cancer cell proliferation, cell cycle progression, apoptosis, and senescence (Karni-Schmidt et al., 2016; Wang et al., 2019b), while USP7 is a critical regulator of this circuitry and tightly controls the stabilities of these proteins, thereby contributing to cancer initiation, progression, and metastasis (Bhattacharya et al., 2018; Rawat et al., 2019). The gene discussed is MDM4; the disease is cancer.