SLC25A46 is a mitochondrial outer membrane protein that plays a critical role in mitochondrial dynamics and organization 1. As the mammalian orthologue of yeast Ugo1, SLC25A46 functions as a mitochondrial carrier family protein essential for regulating the balance between mitochondrial fusion and fission 1. The protein interacts with key fusion machinery including MFN1/2 and OPA1, and coordinates with the MICOS complex to maintain cristae architecture and facilitate proper mitochondrial lipid homeostasis through interaction with the ER membrane protein complex EMC 12. Loss of SLC25A46 function results in mitochondrial hyperfusion, abnormal cristae structure, and impaired cellular respiration 1. SLC25A46 mutations cause severe neurodegenerative diseases, including Leigh syndrome, cerebellar ataxia, optic atrophy, Charcot-Marie-Tooth disease, and pontocerebellar hypoplasia type 1 134. Mouse models demonstrate that SLC25A46 deficiency causes widespread mitochondrial dysfunction affecting the nervous system, muscle, and other organs, with phenotypes including neurodegeneration, motor impairment, and premature mortality 53. Gene therapy using AAV-Slc25a46 successfully rescues these pathological features, demonstrating therapeutic potential for SLC25A46-related mitochondrial disorders 6.