SLC25A12 encodes a mitochondrial electrogenic aspartate/glutamate antiporter that mediates the malate-aspartate shuttle, promoting aspartate efflux while facilitating glutamate and proton entry into mitochondria 1234. The transporter also exchanges L-cysteinesulfinate with glutamate or aspartate, supporting amino acid metabolism 1. SLC25A12 lacks transport activity for glutamine or GABA 4, though related mitochondrial activity can indirectly affect GABA sequestration through Aralar-mediated mechanisms 5. Disease relevance: SLC25A12 variants are associated with autism spectrum disorder (ASD) risk; meta-analyses show rs2056202 and rs2292813 polymorphisms significantly reduce ASD susceptibility 67. Additionally, SLC25A12 mutations cause developmental and epileptic encephalopathy 39 with leukodystrophy 8. Clinical significance: Genetic variants in SLC25A12 represent identifiable molecular markers for ASD risk stratification 9, and pathogenic mutations warrant screening in pediatric neurological disorders 10. The gene's critical role in mitochondrial bioenergetics and ATP synthesis links SLC25A12 dysfunction to broader neurological dysfunction.