SLC25A4 encodes the mitochondrial ADP/ATP antiporter (ANT1), a critical transporter that exchanges cytoplasmic ATP for mitochondrial ADP across the inner mitochondrial membrane to fuel cellular energy metabolism 1. Operating via an alternating access mechanism, SLC25A4 maintains ATP supply for the cell while importing ADP for oxidative phosphorylation 2. Beyond its canonical antiporter function, SLC25A4 regulates mitochondrial thermogenesis through proton transport activity and participates in mitochondrial permeability transition pore function, making it a master regulator of energy output versus heat production 3. SLC25A4 also promotes mitophagy independently of its antiporter activity, supporting mitochondrial quality control 2. Pathogenic SLC25A4 variants cause autosomal dominant/recessive mitochondrial DNA maintenance defects, including mitochondrial DNA depletion syndromes and progressive external ophthalmoplegia, due to impaired nucleotide pool maintenance 2. Loss of ANT1 function increases cellular senescence and contributes to idiopathic pulmonary fibrosis pathogenesis 4. Post-translational modifications regulate SLC25A4 activity: S-nitrosylation impairs cardiac mitochondrial function in heart failure 3, while succinylation promotes osteoporosis progression 5. SLC25A4 upregulation mediates anti-cancer effects in hepatocellular carcinoma through NAD+-dependent metabolic remodeling 6.