SENP1 is a crucial SUMO-specific protease that catalyzes two essential functions in the SUMO pathway: processing SUMO precursors into mature forms and deconjugating SUMO proteins from target substrates 1. The enzyme plays pivotal roles in multiple cellular processes through its desumoylation activity. In metabolic regulation, SENP1 controls mitochondrial function by desumoylating Sirt3, enhancing its deacetylase activity and promoting fatty acid oxidation during fasting stress 2. SENP1 also regulates cell cycle progression, as lactate directly inhibits SENP1 by binding its zinc-containing active site, leading to APC4 SUMOylation and efficient mitotic exit 3. In cardiovascular disease, SENP1 prevents myocardial fibrosis through HSP90ab1 desumoylation and protects against hypoxic pulmonary hypertension via FIS1 desumoylation, which maintains mitochondrial integrity 45. SENP1 demonstrates therapeutic potential in acute kidney injury by coupling with AMPK activation to reduce mitochondrial oxidative stress 6. However, SENP1 can promote tumorigenesis, as seen in acute myeloid leukemia where it activates AKT signaling through HDAC2 desumoylation 7. These findings establish SENP1 as a critical regulator of cellular homeostasis with both protective and pathological roles depending on the cellular context.