Erythroferrone (ERFE)

Erythroferrone is a secreted protein hormone encoded by the ERFE gene (also known as FAM132B or C1QTNF15) and is primarily produced by erythroblasts in response to erythropoietin stimulation. It is the principal hormonal regulator of iron supply for new red blood cell production: ERFE suppresses hepatic expression of hepcidin, the master hormone of systemic iron homeostasis, by inhibiting bone morphogenetic protein (BMP) signaling pathways in the liver. This suppression increases intestinal iron absorption and mobilization of iron stores to support hemoglobin synthesis during periods of increased erythropoiesis, such as after blood loss or in hemolytic anemias. Pathologically excessive ERFE production, especially in conditions of ineffective erythropoiesis (such as β-thalassemia), leads to chronically suppressed hepcidin and secondary iron overload. Erythroferrone may also have metabolic roles in lipid regulation under its alternative name myonectin. The ERFE pathway is an emerging therapeutic target and biomarker in diseases of iron metabolism, though no approved drugs target it as of 2024.

Other names

C1QTNF15CTRP15FAM132BMyonectinComplement C1q tumor necrosis factor-related protein 15Family with sequence similarity 132 member Bprotein FAM132B

Inhibition of hepcidin expression (main physiological effect); mechanism in drug context would be antibody-mediated blockade of ERFE to prevent hepcidin suppression