SLC25A12 encodes a mitochondrial electrogenic aspartate/glutamate antiporter that mediates the exchange of aspartate for glutamate and protons, functioning as a core component of the malate-aspartate shuttle to support mitochondrial energy metabolism. The transporter also facilitates uptake of L-cysteinesulfinate by mitochondria in exchange for glutamate and protons. At the population level, this gene is LoF-tolerant; however, rare pathogenic variants cause developmental and epileptic encephalopathy 39 with leukodystrophy, demonstrating clinical significance in disease contexts distinct from population-level constraint. Genetic variants in SLC25A12 have been associated with autism spectrum disorder (ASD) risk. Meta-analyses show that the rs2292813 and rs2056202 polymorphisms are significantly associated with ASD, with family-based studies demonstrating stronger associations than case-control designs 123. Variants of unknown significance in SLC25A12 have also been identified in pediatric neurological disorders 4. Because SLC25A12 supports mitochondrial ATP synthesis and cellular metabolic functions, its dysfunction may contribute to neurodevelopmental pathology through impaired energy production and excitotoxicity.