Frataxin (FXN) is a nuclear-encoded mitochondrial protein essential for iron-sulfur (Fe-S) cluster biogenesis 1. As an iron chaperone, FXN modulates RNA-binding activity of ACO1 2 and participates directly in Fe-S cluster assembly, contributing to cellular iron homeostasis and oxidative stress resistance 3. FXN deficiency impairs Fe-S-containing polymerase activity, causing replication stress, DNA damage, and cellular senescence 4. Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, results from GAA repeat expansions in FXN intron 1 that silence frataxin transcription 5. This causes mitochondrial dysfunction, reactive oxygen species overproduction, and altered iron metabolism 6. FRDA manifests as progressive sensory and spinocerebellar ataxia with hypertrophic cardiomyopathy—the leading cause of mortality—plus scoliosis and diabetes 5. Notably, hypoxia restores Fe-S cluster synthesis through HIF-independent mechanisms, and reduced oxygen exposure attenuates ataxia progression in mouse models 3. Omaveloxolone, an NRF2 activator, represents the first FDA-approved FRDA treatment 6. Gene editing approaches removing expanded GAA repeats or flanking repressed chr9 restore FXN expression and reverse disease pathology in neuronal models 7. Additional therapeutic strategies targeting multiple disease pathways are under development 6.