Alongside the SLC11 family of proton-coupled metal transporters, ferroportin allows the accumulation of iron from the diet. Whilst SLC11A2 functions on the apical membrane, ferroportin acts on the basolateral side of the enterocyte, as well as regulating macrophage and placental iron levels. The predicted topology is of 12 TM domains, with intracellular termini [6], with the functional transporter potentially a dimeric arrangement [1-2]. Ferroportin is essential for iron homeostasis [4]. Ferroportin is expressed on the surface of cells that store and transport iron, such as duodenal enterocytes, hepatocytes, adipocytes and reticuloendothelial macrophages. Levels of ferroportin are regulated by its association with (binding to) hepcidin, a 25 amino acid hormone responsive to circulating iron levels (amongst other signals). Hepcidin binding targets ferroportin for internalisation and degradation, lowering the levels of iron export to the blood. Novel therapeutic agents which stabilise ferroportin or protect it from hepcidin-induced degradation are being developed as anti-anemia agents. Anti-ferroportin monoclonal antibodies are such an agent.

Hepcidin (HAMP, P81172), cleaved into hepcidin-25 (HAMP, P81172) and hepcidin-20 (HAMP, P81172), is a small protein that increases upon inflammation, binds to ferroportin to regulate its cellular distribution and degradation. Gene disruption in mice results in embryonic lethality [4], while loss-of-function mutations in man are associated with haemochromatosis [3].

* Key recommended reading is highlighted with an asterisk

* McKie AT, Barlow DJ. (2004) The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1). Pflugers Arch, 447 (5): 801-6. [PMID:12836025]

* Montalbetti N, Simonin A, Kovacs G, Hediger MA. (2013) Mammalian iron transporters: families SLC11 and SLC40. Mol Aspects Med, 34 (2-3): 270-87. [PMID:23506870]

1. Aguirre P, Mena N, Tapia V, Arredondo M, Núñez MT. (2005) Iron homeostasis in neuronal cells: a role for IREG1. BMC Neurosci, 6: 3. [PMID:15667655]

2. De Domenico I, Ward DM, Musci G, Kaplan J. (2007) Evidence for the multimeric structure of ferroportin. Blood, 109 (5): 2205-9. [PMID:17077321]

3. De Domenico I, Ward DM, Nemeth E, Vaughn MB, Musci G, Ganz T, Kaplan J. (2005) The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci USA, 102 (25): 8955-60. [PMID:15956209]

4. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC. (2005) The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab, 1 (3): 191-200. [PMID:16054062]

5. Leung DDM, Luan P, Manetta JV, Tang Y, Witcher DR,. (2010) Anti-ferroportin 1 monoclonal antibodies and uses thereof. Patent number: WO2010065496 A1. Assignee: Eli Lilly And Company.. Priority date: 05/12/2008. Publication date: 10/06/2010.

6. Rice AE, Mendez MJ, Hokanson CA, Rees DC, Björkman PJ. (2009) Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J Mol Biol, 386 (3): 717-32. [PMID:19150361]