Erythroferrone (ERFE) is a newly identified erythroid regulator of iron metabolism in recent years. In response to the stimuli of erythropoiesis, erythropoietin (EPO) stimulates the increased production of ERFE in erythroblasts of the bone marrow, which strongly suppresses the transcription of hepcidin in the liver; thereby increases iron absorption from dietary to blood through stabilizing the iron exporter ferroportin 1 (FPN1). Plasma iron is critical for erythropoiesis, and more iron is needed for heme and hemoglobin synthesis to meet the demands of increased erythropoiesis. ERFE in the blood plays an important role in ensuring stable iron supply during erythropoiesis. This review focuses on the discovery of ERFE in phlebotomy and hypoxia, and its gene is Fam132b with the coding sequence of 10 kb. ERFE protein is a glycol protein which belongs to the C1q/TNF-related protein family, and there are 340 and 354 amino acids in mouse and human, respectively. It has been reported that Fam132b mRNA was detected in colon, skeletal muscle, brain, heart and other tissues, while it was rich in bone marrow after phlebotomy. It has been shown that ERFE plays important roles in glucose and fat metabolism, erythropoiesis and iron metabolism through hepcidin and transferrin receptors. Moreover, recent advances in relationships between ERFE dysregulation and diseases including β-thalassemia and chronic kidney disease, as well as the detection of ERFE in clinic and fundamental researches, give a further understanding the role of EPO/ERFE/hepcidin-FPN1 in regulating iron metabolism to provide a potential therapeutic target for treating diseases with iron metabolism disorders.