Physiological iron-binding proteins and transporters

The group of physiological iron-binding proteins and transporters constitutes a functional network including transferrin, ferritin, ferroportin, and the transferrin receptor, which collectively maintain systemic and cellular iron homeostasis (StatPearls, NBK448027). Transferrin is the primary protein for transporting iron in the plasma, while ferritin serves as the major intracellular storage vessel to prevent iron-mediated oxidative damage (UniProt P02787, P02792). Cellular iron entry is primarily mediated by the transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1), whereas ferroportin is the sole known mammalian iron exporter (PubMed: 25533013). These proteins are central to the pathophysiology of various conditions, including iron-deficiency anemia, hereditary hemochromatosis, and certain cancers that exhibit an "iron-addicted" phenotype (NIH, Iron Fact Sheet). Pharmacological interventions targeting this system include iron supplements for deficiency, chelating agents for overload, and novel therapeutics like hepcidin mimetics that regulate iron flux by inhibiting ferroportin (PubMed: 33055348). These proteins also play a role in the innate immune response by sequestering iron from pathogens, a process known as nutritional immunity (PubMed: 26048254). In neurodegenerative diseases, the failure of these transport and storage mechanisms can lead to toxic iron accumulation in the brain (PubMed: 30630115).

Other names

Iron metabolism proteinsIron regulatory proteinsIron homeostasis proteinsIron transporters and storage proteinsIron-binding proteins

The mechanisms of action include direct iron supplementation to increase systemic iron availability, chelation of excess iron to prevent tissue damage, and the modulation of iron export or uptake through the targeting of specific transporters (e.g., ferroportin) or receptors (e.g., transferrin receptor) (StatPearls, NBK448027; PubMed: 33055348).