Frataxin (mitochondrial) (FXN)

Frataxin is a small, highly conserved mitochondrial protein encoded by the FXN gene. It plays a critical role in mitochondrial iron-sulfur cluster biosynthesis and iron homeostasis, functioning as an iron chaperone and possibly as a storage protein. Deficiency of frataxin, most commonly due to expanded GAA repeats in the FXN gene, causes Friedreich’s ataxia, a progressive neurodegenerative disorder. Because low frataxin is the root cause of disease, gene therapy (the transfer of the FXN gene into patient cells) is a major therapeutic strategy. Agents that increase frataxin expression or deliver a functional version of the gene are under intensive clinical investigation; however, precise regulation of frataxin levels is crucial, as both deficiency and overexpression have pathological consequences. In summary, "Frataxin gene transference" is not a molecule or receptor, but rather describes strategies to restore frataxin protein in Friedreich’s ataxia by gene therapy. The true molecular target is the frataxin protein encoded by the FXN gene.

Other names

Frataxin proteinFXNFriedreich ataxia protein

Restoration of frataxin protein levels through gene addition (e.g., AAV, lentivirus, or other vectors); Gene editing (e.g., CRISPR-Cas9 excision of GAA repeats causing gene silencing); Transcriptional activation (HDAC inhibitors, agents that upregulate FXN mRNA); Protection or compensating for mitochondrial dysfunction resulting from frataxin deficiency.