SLC25A22 encodes a mitochondrial glutamate/H+ symporter that mediates the transport of glutamate from the cytosol into the mitochondrial matrix. The transporter plays roles in glucose-stimulated insulin secretion and participates in the malate-aspartate shuttle and neurotransmitter transport pathways. In cancer contexts, SLC25A22 promotes cellular survival and proliferation through metabolic reprogramming. In colorectal cancer cells with KRAS mutations, SLC25A22 drives aspartate synthesis and accumulation of mitochondrial succinate, suppressing DNA demethylation and increasing WNT signaling activation, stemness, and resistance to 5-fluorouracil 12. In glioblastoma, SLC25A22 functions uni-directionally to export glutamate from mitochondria to the cytosol, enhancing glutathione production and promoting radioresistance 3. Upregulation of SLC25A22 is also associated with osteosarcoma progression and metastasis via PTEN pathway inhibition 4. In cervical squamous cell carcinoma, SLC25A22-mediated glutamine metabolism contributes to immune suppression, and targeting SLC25A22 enhances CD8+ T-cell function and anti-PD-1 therapy efficacy 5. Clinically, biallelic loss-of-function mutations in SLC25A22 cause severe autosomal recessive developmental and epileptic encephalopathy, particularly early infantile forms including migrating focal seizures with seizure onset in the first days of life and characteristic suppression-burst EEG patterns 67. Recent transcriptome-wide association studies implicate reduced SLC25A22 expression as an Alzheimer's disease susceptibility factor, with downregulation correlating with hippocampal atrophy 8.