Iron is a vital trace element for almost all organisms, and maintaining iron homeostasis is critical for human health. In mammals, the only known gatekeeper between intestinally absorbed iron and circulatory blood plasma is the membrane transporter ferroportin (Fpn). As such, dysfunction of Fpn or its regulation is a key driver of iron-related pathophysiology. This review focuses on discussing recent insights from high-resolution structural studies of the Fpn protein family. While these studies have unveiled crucial details of Fpn regulation and structural architecture, the associated functional studies have also at times provided conflicting data provoking more questions than answers. Here, we summarize key findings and illuminate important remaining questions and contradictions.
Keywords: iron metabolism; membrane proteins; structural biology; transport.
© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.