Defects in this FPN ‘off-switch’ as a result of hepcidin deficiency or hepcidin resistance due to FPN gain-of-function mutations can eventually lead to systemic iron overload in the form of hemochromatosis [15]–[18], resulting in significant tissue damage and multi-organ failure with limited therapeutic options [19]. The gene discussed is SLC40A1; the disease is Tangier disease.