Iron regulatory proteins (IRPs; also known as IREBs) are RNA-binding proteins that recognize iron responsive elements (IREs) and play an important role in maintaining iron homeostasis in mammalian cells. IREs are conserved cis-regulatory hairpin structures located within the 5’ or 3’ untranslated regions (UTRs) of target mRNAs. IRPs inhibit translation when bound to IREs within the 5’ UTR of mRNA encoding for proteins involved in iron storage, export, and utilization. IRP binding to multiple IREs within the 3’ UTR of transferin receptor 1 (TFR1) mRNA prevents its degradation, thereby augmenting translation of TFR1 and increasing iron uptake into cells (1-3). Dysregulation of IRPs has been associated with human cancers (4-6). IRP1 is a bifunctional protein. In iron replete cells, IRP1 is associated with a 4Fe-4S cluster that keeps IRP1 in a closed conformation, and functions as a cytosolic aconitase catalyzing the conversion of citrate into iso-citrate. In iron deficient cells, IRP1 loses the 4Fe-4S cluster and adopts an open structure with IRE-binding activity (7).