Previous studies have shown that USP48‘s deubiquitinating activity regulates NFκB signaling by stabilizing RelA in the nucleus, which is essential for cancer cell survival.13,23 Additionally, USP48 has been shown to promote tumorigenesis by stabilizing oncoproteins such as Gli1, TRAF2, and Mdm2.12,16,24 Beyond its oncogenic functions, USP48 is also involved in cell cycle progression,14 and its high expression levels in various tumors are closely associated with poor prognosis.15,25 Our study demonstrated that USP48 is a highly specific substrate of activated caspase-3. The gene discussed is MDM2; the disease is cancer.