Usp4 is a member of the ubiquitin-specific protease family of deubiquitinating enzyme. A number of substrates of Usp4 have been identified, including TRIM21, TRAF2, TRAF6, RIG-1, RIP1, PDK1, TAK1 and etc. Usp4-mediated deubiquitination was found to regulate several signaling pathways, including the AKT signaling, RIG-1-mediated antiviral response, TNFα-induced signaling, and the Wnt signaling.