SLC25A18 is a mitochondrial solute carrier protein responsible for transporting glutamate from the cytosol into the mitochondrial matrix via proton symport 1. This glutamate carrier 2 is essential for providing substrates for mitochondrial bioenergetics 2. Mechanism: SLC25A18 mediates L-glutamate transmembrane transport coupled with proton import, participating in the malate-aspartate shuttle and amino acid metabolism. The protein localizes to the mitochondrial inner membrane 3. Disease Relevance: Increased SLC25A18 expression is associated with Alzheimer's disease pathology. In neuronal cells, elevated SLC25A18 expression following Aβ42 exposure increases mitochondrial superoxide anions while decreasing mitochondrial membrane potential, promoting mitochondrial dysfunction and neuronal apoptosis 3. SLC25A18 has been identified as a genetic risk factor for rheumatoid arthritis 4. Additionally, SLC25A18 amplification within the cat eye syndrome critical region may contribute to congenital anorectal, renal, and preauricular anomalies 56. In hyperargininemia models, genetic inactivation of SLC25A18 suppresses mitochondrial dysfunction caused by arginine accumulation 1. Clinical Significance: SLC25A18 represents a potential therapeutic target for neurodegeneration and inflammatory diseases, though therapeutic strategies remain under investigation.