FDX2 (ferredoxin 2) is a mitochondrial [2Fe-2S] cluster-containing protein that serves as an essential electron donor in iron-sulfur cluster biosynthesis. FDX2 functions as a core component of the mitochondrial iron-sulfur cluster (ISC) assembly complex, providing reducing equivalents to reduce persulfide into sulfide during [2Fe-2S] cluster assembly on the scaffold protein ISCU 1. Structurally, FDX2 binds to the ISC complex through two conformations - a 'distal' state where it interacts electrostatically with NFS1, and a 'proximal' state enabling closer positioning for electron transfer to ISCU 2. FDX2 exhibits functional specificity distinct from FDX1, being specifically involved in Fe-S protein maturation rather than steroidogenesis 3. The protein also participates in coenzyme Q biosynthesis by transferring electrons for COQ6-mediated hydroxylation reactions. Disease relevance includes mitochondrial myopathy with episodic presentation, optic atrophy, and reversible leukoencephalopathy (MEOAL), caused by mutations like P144L that impair electron transfer efficiency with ferredoxin reductase 4. FDX2 deficiency leads to cellular senescence, apoptosis, or ferroptosis depending on cellular context, highlighting its critical role in maintaining mitochondrial redox homeostasis 5. Therapeutically, modulating FDX2 levels may benefit Friedreich's ataxia treatment 6.