USP15 is a ubiquitin-specific protease (Baker et al. 1999) reported to act on several substrates. It promotes deubiquitination of monoubiquitinated R-SMADs, indirectly promoting the activation of TGF-beta target genes (Inui et al. 2011). USP15 binds the SMAD7:SMURF2 complex, deubiquitinating and stabilizing the type I TGFBeta receptor (TGFBR1), leading to enhanced TGF-Beta signalling (Eichorn et al. 2012). USP15 deubiquitinates KEAP1, which suppresses the Nrf2 pathway (Villeneuve et al. 2013).