Divalent metal ion transporters DMT1 and FPN are vital for iron transport in enterocytes and for transferrin associated endosomal iron transport in many other cell types. Their dysfunction is associated with anemia, iron overload disorders, neurodegenerative diseases (e.g., Parkinson's disease and Alzheimer’s disease), breast and colorectal cancer and autoimmune and inflammatory diseases (e.g., rheumatoid arthritis). The involvement of DMT1 and FPN in these disorders makes their pharmacological modulation a promising therapeutic strategy. The aim of the project is to determine the structure and to characterize the function of divalent metal ion transporters, providing a framework for the development of small molecule modulators and the comprehension of their mechanism of action. Small molecule modulators and binding proteins will be used as tools for physiological studies of iron transport in the placenta and in bone. In addition, they will serve for the investigation of potential therapeutic strategies against the iron overload disorder hemochromatosis, neurodegenerative diseases and osteoporosis.