SENP7 (SUMO-specific peptidase 7) is a deSUMOylase that catalyzes removal of SUMO2 and SUMO3 conjugates from target proteins, exhibiting particular efficiency in processing poly-SUMO2/3 chains 1. Its catalytic activity depends on a unique Loop1 insertion that confers SUMO2/3 isoform specificity 2. SENP7 functions across multiple biological contexts through protein deSUMOylation: it sustains CD8+ T cell metabolic fitness and antitumor functions by sensing oxidative stress to promote PTEN deSUMOylation and degradation 3, promotes regulatory B cell differentiation and immune evasion in colorectal cancer via SIRT1 deSUMOylation and IL-10 upregulation 4, and coordinates sarcomere assembly by deSUMOylating flightless-1 to regulate myosin heavy chain expression 5. In reproduction, SENP7 programs meiosis architecture and epigenetic landscapes critical for oocyte maturation and embryo survival 6. Additionally, SENP7 interacts with IFI204 in microglia to promote pyroptosis and mitochondrial dysfunction following traumatic brain injury 7. SENP7 itself is regulated as a substrate of the CULLIN3-based E3 ubiquitin ligase adaptor SPOP 8, linking its activity to cancer-associated signaling dysregulation.