Iron is ubiquitous in the environment and in biology. The study of iron biology focuses on physiology and homeostasis-understanding how cells and organisms regulate their iron content, how diverse tissues orchestrate iron allocation, and how dysregulated iron homeostasis leads to common hematological, metabolic, and neurodegenerative diseases. This has provided novel insights into gene regulation and unveiled remarkable links to the immune system.

The regulation and maintenance of systemic iron homeostasis is critical to human health. Iron overload and deficiency diseases belong to the most common nutrition-related pathologies across the globe. It is now well appreciated that the hormonal hepcidin/ferroportin system plays an important regulatory role for systemic iron metabolism. We review recent data that uncover the importance of the cellular iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network in systemic iron homeostasis. We also discuss how the IRE/IRP regulatory system communicates with the hepcidin/ferroportin system to connect the control networks for systemic and cellular iron balance.