SLC25A21 is a mitochondrial inner membrane transporter that mediates counter-exchange of dicarboxylates across the mitochondrial membrane 1. It transports 2-oxoadipate, 2-oxoglutarate, adipate, glutarate, and related metabolites, playing a central role in the catabolism of lysine, hydroxylysine, and tryptophan by facilitating entry of metabolic intermediates into the mitochondria for conversion to acetyl-CoA and citric acid cycle entry 1. SLC25A21 expression is associated with maintaining mitochondrial metabolic homeostasis, including oxidative phosphorylation and biogenesis 2. Beyond basic metabolism, SLC25A21 functions as a tumor suppressor: its downregulation in KRAS-mutant colorectal cancer promotes progression by disrupting α-ketoglutarate efflux and enhancing glutamine anaplerosis 3, while its overexpression in acute myeloid leukemia inhibits cell proliferation and promotes mitochondrial apoptosis 4. In acute kidney injury, reduced SLC25A21 expression impairs mitochondrial function and increases cellular death 2. Germline SLC25A21 mutations are associated with mitochondrial DNA depletion syndrome 18, though complete knockout mice are phenotypically normal, suggesting potential compensation mechanisms 5. SLC25A21 emerges as a prognostic biomarker and potential therapeutic target across multiple disease contexts.