Our data demonstrate decreased Mek1/2-Erk1/2 signaling output in iron overloaded conditions, suggesting that Mek1/2-Erk1/2 signaling is uncoupled from Bmp-Smad1/5/8-mediated hepcidin induction and that it may play an important role in liver diseases characterized by hepatic iron excess. The gene discussed is MAP2K1; the disease is liver disorder.