Structural variability of the ubiquitin specific protease DUSP-UBL double domains

► We demonstrate that DUSP-UBL double domain can exist in different oligomeric states. ► We solve structures of DUSP-UBL from USP15 monomer and dimer. ► We identify structural features that dictate the oligomeric state of DUSP-UBL unit and disposition of constituent domains. ► We analyze the physiological state of USP15.