ENSA (endosulfine alpha) is a protein phosphatase inhibitor with dual regulatory functions in cell cycle control and metabolic signaling. During mitosis, ENSA acts as a PP2A inhibitor when phosphorylated at Ser-67, helping maintain high cyclin-B1-CDK1 activity essential for M phase progression 1. In pancreatic beta cells, ENSA regulates insulin secretion by interacting with sulfonylurea receptors and inhibiting K(ATP) channel currents 2. Recent studies reveal ENSA's role in cancer progression through multiple mechanisms. In pancreatic ductal adenocarcinoma, lactate-induced K63 lactylation of ENSA (ENSA-K63la) inactivates PP2A and activates STAT3/CCL2 signaling, promoting immunosuppressive tumor microenvironments and therapeutic resistance 3. In triple-negative breast cancer, ENSA amplification at chromosome 1.3 drives tumor progression by upregulating cholesterol biosynthesis through SREBP2 via STAT3 activation 4. ENSA is also functional in anucleate platelets, where it participates in the MASTL-ENSA/ARPP19-PP2A pathway and is regulated by cAMP/PKA signaling 5. The ENSA gene maps to chromosome 1 but was initially localized to chromosome 1.3-q31, near a type 1 diabetes susceptibility locus 2.