Sentrin-Specific Protease 7 (SENP7) acts as a SUMO-2/3-specific protease. SENP7 is likely to regulate the metabolism of poly-SUMO-2/3 rather than SUMO-1 conjugation in vivo. SENP7 has a restricted substrate specificity, and displaying paralogue-specific isopeptidase activity. The C-terminal catalytic domain of SENP7 depolymerized poly-SUMO-2 chains but does not have activity against poly-SUMO-1 chains. SENP7 also had isopeptidase activity against di-SUMO-2- and SUMO-2-modified RanGAP1 (Ran GTPase-activating protein 1) but had limited activity against SUMO-1-modified RanGAP1.