UCP2 is a mitochondrial antiporter that exports dicarboxylate intermediates of the Krebs cycle across the inner mitochondrial membrane, thereby regulating energy metabolism and reactive oxygen species (ROS) production. By facilitating the continuous export of oxaloacetate and related four-carbon substrates from the mitochondrial matrix, UCP2 lowers the ATP/ADP ratio and ROS levels, functions distinct from the thermogenic role of UCP1. UCP2 also mediates proton entry into the mitochondrial matrix and regulates glucose metabolism, including glucose-induced mitochondrial fission in hypothalamic neurons that control systemic glucose homeostasis. In disease contexts, UCP2 has emerged as a key player in vascular and metabolic pathology. Endothelial UCP2 is mechanosensitively regulated by fluid shear stress through KLF2 and suppresses atherosclerosis; EC-specific Ucp2 deletion promotes atherosclerotic plaque formation in disturbed flow models 1. In pancreatic tissue, upregulated UCP2 drives chr11 pancreatitis progression by promoting macrophage-to-myofibroblast transition via the Sirt1/Smad3 pathway, with UCP2 knockout reducing fibrosis 2. UCP2 downregulation is observed in diabetic retinopathy, where overexpression restores the NAD+-dependent SIRT3 axis to mitigate hyperglycemia-induced oxidative stress and endothelial senescence 3. Genetic variants in UCP2 are associated with schizophrenia susceptibility in Turkish populations 4, and altered UCP2 expression is observed in bipolar disorder 5. These findings position UCP2 as a potential therapeutic target in atherosclerotic, pancreatic, diabetic, and neuropsychiatric diseases, though approved therapies targeting UCP2 remain unavailable.