Role of BMP6 and TMPRSS6 in hepcidin production. A model for adequate hepcidin regulation is based on the balance between BMP6 and TMPRSS6. In normal conditions (top middle), hepcidin production and iron levels are adequate because of the balanced activity of TMPRSS6 and BMP6. In iron deficiency (bottom left), TMPRSS6 activity is increased whereas BMP6 is low because of low tissue iron: this combination results in low hepcidin expression. In iron overload (bottom right), TMPRSS6 activity must be repressed (although the mechanisms are unknown), whereas BMP6 expression is enhanced by increased tissue iron.