SSideroflexins (SCL56) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function but, since their first description, they were thought to be metabolite transporters maybe required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 was recently identified as the previously unknown mitochondrial transporter of serine but pending questions on the molecular function of sideroflexins remain, especially their link with iron. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse - but growing - evidence linking sideroflexins to iron homeostasis and iron-sulfur proteins. Since an imbalance in iron homeostasis favors retinal degeneration, we also investigate the relationships between sideroflexins, iron and retinal degeneration. Research on Sideroflexins’ functions constitute an emerging research field of great interest and will certainly lead to main discoveries on mitochondrial physiopathology