This study investigates the role of hepcidin in iron homeostasis by generating transgenic mice that overexpress hepcidin under the control of the liver-specific transthyretin promoter. The majority of these transgenic mice exhibit severe microcytic hypochromic anemia, decreased body iron levels, and early postnatal lethality. The authors found that the severity of the anemia is correlated with the fetal expression of the transgene. They also confirmed that the absence of hepcidin, as observed in *Usf2* knockout mice, leads to iron overload. These findings strongly support the role of hepcidin as a key regulator of iron transport and suggest that hepcidin plays a central role in maintaining iron homeostasis. The transgenic models of hepcidin overexpression and deficiency provide valuable tools for further investigating iron homeostasis and potential therapeutic interventions.This study investigates the role of hepcidin in iron homeostasis by generating transgenic mice that overexpress hepcidin under the control of the liver-specific transthyretin promoter. The majority of these transgenic mice exhibit severe microcytic hypochromic anemia, decreased body iron levels, and early postnatal lethality. The authors found that the severity of the anemia is correlated with the fetal expression of the transgene. They also confirmed that the absence of hepcidin, as observed in *Usf2* knockout mice, leads to iron overload. These findings strongly support the role of hepcidin as a key regulator of iron transport and suggest that hepcidin plays a central role in maintaining iron homeostasis. The transgenic models of hepcidin overexpression and deficiency provide valuable tools for further investigating iron homeostasis and potential therapeutic interventions.