This study investigates the role of hepcidin in iron homeostasis using transgenic mice. The researchers generated transgenic mice expressing hepcidin under the control of the liver-specific transthyretin promoter. These mice exhibited severe microcytic hypochromic anemia, indicating that hepcidin may act as a regulator of iron homeostasis. The study also examined the iron-overload phenotype in Usf2 knockout mice, which showed similar characteristics to human hereditary hemochromatosis. However, when the same phenotype was observed in another Usf2 knockout model, iron metabolism was normal, suggesting that the iron-overload phenotype in the first model was not due to USF2 deficiency but rather to the absence of hepcidin. The transgenic mice overexpressing hepcidin showed severe iron deficiency anemia, supporting the hypothesis that hepcidin is a key regulator of iron homeostasis. The study highlights the importance of hepcidin in regulating iron transport and suggests that variations in hepcidin levels could lead to either iron deficiency or overload. The findings provide valuable insights into the molecular mechanisms of hepcidin action and its role in iron homeostasis.This study investigates the role of hepcidin in iron homeostasis using transgenic mice. The researchers generated transgenic mice expressing hepcidin under the control of the liver-specific transthyretin promoter. These mice exhibited severe microcytic hypochromic anemia, indicating that hepcidin may act as a regulator of iron homeostasis. The study also examined the iron-overload phenotype in Usf2 knockout mice, which showed similar characteristics to human hereditary hemochromatosis. However, when the same phenotype was observed in another Usf2 knockout model, iron metabolism was normal, suggesting that the iron-overload phenotype in the first model was not due to USF2 deficiency but rather to the absence of hepcidin. The transgenic mice overexpressing hepcidin showed severe iron deficiency anemia, supporting the hypothesis that hepcidin is a key regulator of iron homeostasis. The study highlights the importance of hepcidin in regulating iron transport and suggests that variations in hepcidin levels could lead to either iron deficiency or overload. The findings provide valuable insights into the molecular mechanisms of hepcidin action and its role in iron homeostasis.