Mitochondrial glutamate carrier 1 (SLC25A22)

SLC25A22 (mitochondrial glutamate carrier 1) is a member of the solute carrier family 25 that catalyzes the import of glutamate into the mitochondrial matrix coupled with proton co-transport. It is primarily expressed in neural and peripheral tissues, with crucial functions in energy metabolism, cellular homeostasis, and glutaminolysis—especially in astrocytes and KRAS-mutant colorectal cancer cells. Pathogenic variants result in severe early-onset epileptic encephalopathies and metabolic disorders, while upregulation in tumor cells correlates with cancer progression and poor prognosis. SLC25A22 is being investigated as a synthetic lethal target in specific cancer contexts but currently has no approved targeted therapeutics. The protein is essential for normal neuronal, hepatic, and systemic metabolic functions, and both genetic deficiency and pharmacological inhibition pose significant safety risks.

Other names

SLC25A22GC1GC-1NET44FLJ13044Early infantile epileptic encephalopathy 3 (EIEE3, DEE3)Glutamate/H(+) symporter 1Mitochondrial glutamate carrier 1Solute carrier family 25 member 22

Inhibitors or downregulation: Suppression of SLC25A22 limits glutamate import into mitochondria, thereby restricting glutaminolysis and energy production in KRAS-mutant cancer cells, reducing proliferation and stemness. Gene therapy or replacement: Hypothetical, for loss-of-function mutations causing encephalopathy, aiming to restore transporter function.