Erfe, also known as erythroferrone, is the main erythroid regulator of hepcidin, a homeostatic hormone controlling plasma iron levels and total body iron [1]. It functions in the iron homeostasis pathway. When erythropoietin stimulates new red blood cell production, it increases Erfe synthesis in bone marrow erythroblasts. Erfe then suppresses hepcidin synthesis, mobilizing cellular iron stores for heme and hemoglobin synthesis [1]. Genetic models, like mouse models, are valuable for studying its function.

In ineffective erythropoiesis, overproduction of Erfe by expanded erythroblast populations suppresses hepcidin and causes iron overload, even in non-transfused patients. This indicates Erfe may be a biomarker of ineffective erythropoiesis and a target for treating its systemic effects [1]. In congenital dyserythropoietic anemias (CDAs), which are ineffective erythropoiesis conditions, the role of Erfe in mediating hepatic iron overload has been studied [2]. In cachectic cancer patients' muscle biopsies and murine cachexia models, Erfe is upregulated, and knockdown of Erfe reduces muscle wasting, suggesting its role in cancer cachexia-related muscle atrophy [3].

In conclusion, Erfe plays a crucial role in iron homeostasis, especially in erythropoiesis-related iron regulation. Its overproduction in ineffective erythropoiesis-related diseases like CDAs contributes to iron overload. In cancer cachexia, Erfe is involved in muscle atrophy. Studies on Erfe using models like mouse models help in understanding these disease mechanisms and potentially developing new treatments.

References:

1. Srole, Daniel N, Ganz, Tomas. 2020. Erythroferrone structure, function, and physiology: Iron homeostasis and beyond. In Journal of cellular physiology, 236, 4888-4901. doi:10.1002/jcp.30247. https://pubmed.ncbi.nlm.nih.gov/33372284/

2. Iolascon, Achille, Andolfo, Immacolata, Russo, Roberta. . Congenital dyserythropoietic anemias. In Blood, 136, 1274-1283. doi:10.1182/blood.2019000948. https://pubmed.ncbi.nlm.nih.gov/32702750/

3. Mina, Erica, Wyart, Elisabeth, Sartori, Roberta, Silvestri, Laura, Porporato, Paolo E. 2023. FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy. In Cell reports. Medicine, 4, 101306. doi:10.1016/j.xcrm.2023.101306. https://pubmed.ncbi.nlm.nih.gov/38052214/