Ferroportin (SLC40A1) is an iron transporter suggested to play roles in intestinal iron absorption and cellular iron release. To date, Ferroportin is the only known mammalian iron exporter and is essential for transport of iron from one cell type to another¹.

Ferroportin has 9-12 transmembrane domains. The topology of the transporter has not been defined with precision and the number of transmembrane domains is still under scrutiny. Studies indicate that the amino terminus of Ferroportin is cytosolic. The location of the carboxyl-terminal, however, is unclear. A second controversial issue regarding Ferroportin structure is whether Ferroportin is a monomer or dimer. Many reports using similar approaches including chromatography, cross-linking and physical techniques such as birefringence, have led to contrasting results².

Ferroportin is found in all the tissues where major iron flows are regulated, including duodenal enterocytes, placental trophoblast, macrophages, and hepatocytes³.

Mutations that result in defective Ferroportin transport activity will lead to the phenotype of “classic” Ferroportin disease, which is macrophage iron loading and normal to low transferrin saturation². Expression of mutant Ferroportin in some cultured cell types results in defects in Ferroportin trafficking where the mutant protein never reaches the cell surface⁴. In other cell types, the mutant Ferroportin was shown to accumulate at the cell surface but had defective transport activity⁵.