Ludwiczek et al.[1] now present support for the notion that the product of the hereditary hemochromatosis gene HFE1 and hepcidin levels determine body iron homeostasis. The authors determined the genetic heterogeneity in HFE1 expression in the liver and duodenum of mice and found correlations between its expression and that of other iron regulatory proteins. They also looked at the effects of low and high dietary iron intake in mice and found effects, but less so than those of genetic heterogeneity. Low iron markedly decreased hepcidin expression. The authors speculate whether hepcidin influences HFE1 expression, perhaps through effects on iron homeostasis. The authors’ primary focus was not on hepcidin; however, the protein has gained notoriety recently that warrants comment.