Iron metabolism is essential for sustaining mammalian homeostasis. Iron uptake and distribution is a highly regulated process in mammalian cells that is monitored by two iron sensing proteins: IRP-1 and -2 (iron regulatory protein-1 and -2), also known as iron responsive element-binding protein-1 and -2 (IRE-BP-1 and -2) or aconitase 1 and 2. IRP-1 and IRP-2 are important soluble regulatory factors that mediate iron uptake and storage in mammalian cells. They are capable of either repressing translation or enhancing mRNA stability by associating with stem-loop motifs known as iron-responsive elements (IREs). IRPs respond to stress mediators, iron concentration and signaling factors, including nitrogen monoxide, cytokines and hydrogen peroxide.