SLC25A3 encodes the mitochondrial phosphate carrier (PiC), a solute carrier protein localized to the mitochondrial inner membrane with dual transport functions. Primarily, SLC25A3 mediates proton-coupled symport of inorganic phosphate ions essential for mitochondrial oxidative phosphorylation and ATP synthesis 1. Additionally, SLC25A3 transports copper ions in anionic copper(I) complex forms to maintain mitochondrial copper homeostasis and support cytochrome c oxidase assembly 2. Beyond its canonical transport role, SLC25A3 regulates mitochondrial dynamics through copper-dependent control of flickering-induced Opa1 processing, a mechanism critical for mitochondrial safeguard against excessive fusion 3. SLC25A3 also negatively regulates NLRP3 inflammasome activation by interacting with NLRP3 and promoting its ubiquitination, thereby modulating innate immune responses 4. Clinically, SLC25A3 mutations cause mitochondrial phosphate carrier deficiency, presenting with lactic acidosis, cardiac hypertrophy, diastolic dysfunction, calcium homeostasis imbalance, and premature mortality 5. SLC25A3 expression patterns are altered in hepatocellular carcinoma and associated with poor prognosis 6, while dysregulation contributes to steroid-induced osteonecrosis through altered cuproptosis 7. The gene exhibits unusual alternative splicing patterns in vertebrates 8.