SLC25A5 (ANT2) is a mitochondrial ADP/ATP antiporter that mediates bidirectional adenine nucleotide transport across the inner mitochondrial membrane, importing ADP for ATP synthesis and exporting ATP to fuel cellular processes 1. Operating through an alternating access mechanism, SLC25A5 cycles between cytoplasmic-open and matrix-open conformations to exchange these substrates. Beyond its primary ATP-ADP exchange function, SLC25A5 regulates mitochondrial permeability transition pore opening, contributing to apoptotic pathways 1. The protein also functions as a proton transporter to promote mitochondrial uncoupling and thermogenesis, with activity regulated by free fatty acids 2. SLC25A5 expression is reduced in idiopathic pulmonary fibrosis, where loss contributes to epithelial cell senescence and impaired regenerative capacity 3. In osteosarcoma, elevated SLC25A5 promotes drug resistance and CD8+ T cell exhaustion within the tumor microenvironment 4. SLC25A5 is upregulated in extracellular vesicles derived from therapy-resistant tumors, facilitating bioenergetic reprogramming and treatment resistance 5. Post-translational modifications, including lysine β-hydroxybutyrylation under ketogenic stress, stabilize SLC25A5 and enhance lipogenesis in alcoholic liver disease 2. These pleiotropic functions position SLC25A5 as a critical regulator of mitochondrial metabolism, cell fate, and tumor biology.