Usp2, or ubiquitin-specific processing protease 2, is a multifunctional deubiquitinating enzyme. It modulates cell cycle progression, carcinogenesis, and energy metabolism. It is involved in pathways such as the regulation of cyclins, Aurora-A, p53 signaling, and the CLOCK/BMAL1 complex-related rhythmic gene expression [2].

Usp2 knockout mice exhibit changes in locomotion and male fertility, suggesting its roles in the central nervous system and male genital tract [2].

In cancer, depletion of Usp2 causes endoplasmic reticulum-associated degradation of PD-L1, enhancing antitumor immunity by increasing CD8+ T cells infiltration and reducing immunosuppressive cell infiltration [1]. Also, targeting the Usp2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression [3]. Inhibition of Usp2 can enhance TRAIL-mediated cancer cell death through downregulation of survivin [5]. Moreover, Usp2 inhibition can prevent infection with ACE2-dependent coronaviruses in vitro and protect against SARS-CoV-2 in mice [4].

In conclusion, Usp2 is a crucial deubiquitinating enzyme with diverse functions. Its study using knockout mouse models has revealed its significance in cancer immunotherapy, autophagy regulation in cancer, and protection against ACE2-dependent coronavirus infections. These findings provide potential therapeutic targets for related diseases.