Notably, recent studies have demonstrated that epigenetic modifications work with genetic mechanisms and play critical roles in carcinogenesis and progression and treatment resistance of cancers with different genetic backgrounds and oncogenic drivers, which makes them attractive and novel therapeutic candidate targets for cancers [5, 6]. Ubiquitin-specific peptidase 22 (USP22), a subunit of the human SAGA (Spt-Ada-Gcn5-Acetyltransferase) complex, is an ubiquitin hydrolase, catalyzing the removal of the mono-ubiquitin moiety from histone H2B (H2Bub1) [6, 7]. The gene discussed is USP22; the disease is cancer.