(A) IRPs dynamically bind IREs in the UTRs of target mRNAs to regulate the expression of proteins important in iron metabolism. When iron is sufficient, IRP1 and IRP2 do not bind mRNA because (a) IRP1 binds Fe-S clusters, preventing IRP1 from binding to the IREs on target mRNAs, and (b) IRP2 is degraded in a process dependent on FBXL5. In ID, binding of IRPs to IREs located at the 5′-UTR of the transcripts causes steric blockage of ribosomal entry and prevention of translation (FPN, FTN). Binding of IRPs to IREs located on the 3′-UTR of target mRNAs increases stability of the transcript and thus increases translation (TFR1, DMT1). Accordingly, this leads to upregulated translation of iron acquisition proteins such as TFR1 and DMT1 and downregulation of proteins that bind or export iron such as FTN or FPN. (B) In severe ID, iron is preserved for vital processes via a mechanism called the iron conservation pathway. Critically low iron induces upregulation of TTP that binds AU-rich elements (AREs) in the 3′-UTR of target mRNAs. Under critically low iron conditions, ARE-bound TTP recruits CNOT1, a member of the CCR4-NOT deadenylase complex, to promote degradation of target mRNAs. Multiple TTP target mRNAs encode iron-binding proteins that could sponge the limited iron available in the cell, such as mitochondrial Fe-S–containing proteins, necessitating their translational downregulation in severe ID.