SLC25A26 encodes the mitochondrial S-adenosylmethionine carrier (SAMC), which functions as an antiporter that mediates the exchange of cytosolic S-adenosylmethionine (SAM) for mitochondrial S-adenosylhomocysteine (SAH) 1. This transport is essential for mitochondrial methylation processes, including the regulation of replication, transcription, translation, and biosynthesis of cofactors such as ubiquinone and lipoate 1. The protein maintains cellular homeostasis by controlling mitochondrial SAM availability, which affects mitochondrial DNA methylation and respiratory complex function 2. SLC25A26 is regulated by FBXO24-mediated ubiquitination for protein stability during cellular processes like spermiogenesis 3. Disease relevance includes combined oxidative phosphorylation deficiency 28 (COXPD28), where compound heterozygous mutations (p.A66E, p.A12P) significantly reduce SLC25A26 expression and cause mitochondrial dysfunction 4. In cancer, SLC25A26 is frequently downregulated through promoter hypermethylation and FOXD3-mediated repression 25. Overexpression impairs cancer cell function by promoting mitochondrial DNA hypermethylation, reducing ATP production, and inducing apoptosis 2. The gene shows aberrant expression in multiple cancers including cervical, liver, and low-grade gliomas, suggesting potential as a therapeutic target 6.