Nai et al. (2011) demonstrated that TMPRSS6 V736A directly modulates HAMP expression in vitro and that healthy individuals with the homozygous substitution had lower levels of serum hepcidin, higher serum iron and higher transferrin saturation. Taken together, these studies clearly establish TMPRSS6/matriptase-2 as an important regulator of iron homeostasis in humans. A recent review focused more on the anemia induced by matriptase-2 mutations is complementary to the current review (De Falco et al., 2013). Here, TMPRSS6 is linked to anemia (phenotype).