Systemic iron handling proteins

Systemic iron handling proteins comprise a coordinated network of molecules that regulate the absorption, transport, storage, and recycling of iron to maintain physiological homeostasis (NIH, 2024). The central orchestrator of this system is hepcidin, a liver-derived peptide hormone that controls iron flux by binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter (MDPI, 2024). Other critical components include transferrin, which transports iron in the plasma; transferrin receptors (TfR1), which facilitate cellular iron uptake; and ferritin, which serves as the primary intracellular iron storage protein (NIH, 2024). Dysregulation of these proteins leads to significant pathologies, such as iron-deficiency anemia, anemia of chronic disease (where hepcidin is overexpressed), and hereditary hemochromatosis (where hepcidin is deficient) (ResearchGate, 2024). Therapeutic strategies targeting this axis include hepcidin mimetics (e.g., rusfertide) for iron overload disorders, hepcidin inhibitors (e.g., lexaptepid pegol) for anemia, and TMPRSS6 inhibitors (e.g., SLN124) to modulate endogenous hepcidin levels (NIH, 2024). These interventions aim to restore balanced iron distribution, prevent oxidative tissue damage from labile iron, and improve erythropoietic efficiency (MDPI, 2024).

Other names

Iron homeostasis proteinsIron metabolism proteinsIron regulatory proteins (systemic)Hepcidin-ferroportin axis proteinsIron transport and storage proteins

Drugs targeting systemic iron handling proteins function by modulating the hepcidin-ferroportin axis to control iron export, inhibiting upstream regulators like TMPRSS6 to increase hepcidin expression, or directly chelating iron to reduce the labile iron pool and prevent oxidative damage.