hFpn structure depicting clinically relevant mutant residues. (A) A side view of hFpn in its outward-facing state, with the N-terminus on the left and C-terminus on the right. (B) A top-down view of hFpn in its outward-facing state. D270V is not modeled because it is located in the unstructured intracellular loop of Fpn. The red/pink color denotes mutants with impaired hepcidin binding, and the green color denotes mutants with intact hepcidin binding, but variably impaired hepcidin-dependent ubiquitination. For simplicity, the mild and borderline mutants are labeled with the same light color.