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The liver hormone hepcidin is the master regulator of systemic iron balance by controlling the degradation and function of the sole known mammalian iron exporter ferroportin. Liver hepcidin expression is coordinately regulated by several signals that indicate the need for more or less iron, including plasma and tissue iron levels, inflammation, and erythropoietic drive. Most of these signals regulate hepcidin expression by modulating the activity of the bone morphogenetic protein (BMP)\u2010SMAD pathway, which controls hepcidin transcription. Genetic disorders of iron overload and iron deficiency have identified several hepatocyte membrane proteins that play a critical role in mediating the BMP\u2010SMAD and hepcidin regulatory response to iron. However, the precise molecular mechanisms by which serum and tissue iron levels are sensed to regulate BMP ligand production and promote the physical and\/or functional interaction of these proteins to modulate SMAD signaling and hepcidin expression remain uncertain. This critical commentary will focus on the current understanding and key unanswered questions regarding how the liver senses iron levels to regulate BMP\u2010SMAD signaling and thereby hepcidin expression to control systemic iron homeostasis.<\/jats:p>","DOI":"10.1002\/dvdy.372","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T03:09:46Z","timestamp":1621134586000},"page":"26-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions"],"prefix":"10.1002","volume":"251","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-2442","authenticated-orcid":false,"given":"Allison L.","family":"Fisher","sequence":"first","affiliation":[{"name":"Division of Nephrology, Program in Membrane Biology, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts 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