Heme oxygenase 1 (Hmox1) is essential for mammalian iron reutilization. This study shows that mice lacking functional Hmox1 develop anemia and accumulate iron in the liver and kidneys, leading to oxidative damage and chronic inflammation. Hmox1 facilitates the release of iron from hepatic and renal cells, playing a key role in iron homeostasis. The study describes a mouse model of human iron metabolic disorders. Iron is crucial for many cellular processes and is primarily reutilized from heme in cells. Hmox1, which breaks down heme into biliverdin, carbon monoxide, and free iron, is involved in iron recycling. Hmox1 deficiency leads to serum iron deficiency and tissue iron overload, indicating its importance in iron homeostasis. The study also highlights the role of Hmox1 in antioxidant defense and iron recycling. The results suggest that Hmox1 is crucial for the release of iron from tissue stores, and its absence leads to iron overload and related pathologies. The study provides a mouse model for understanding human iron metabolic disorders.Heme oxygenase 1 (Hmox1) is essential for mammalian iron reutilization. This study shows that mice lacking functional Hmox1 develop anemia and accumulate iron in the liver and kidneys, leading to oxidative damage and chronic inflammation. Hmox1 facilitates the release of iron from hepatic and renal cells, playing a key role in iron homeostasis. The study describes a mouse model of human iron metabolic disorders. Iron is crucial for many cellular processes and is primarily reutilized from heme in cells. Hmox1, which breaks down heme into biliverdin, carbon monoxide, and free iron, is involved in iron recycling. Hmox1 deficiency leads to serum iron deficiency and tissue iron overload, indicating its importance in iron homeostasis. The study also highlights the role of Hmox1 in antioxidant defense and iron recycling. The results suggest that Hmox1 is crucial for the release of iron from tissue stores, and its absence leads to iron overload and related pathologies. The study provides a mouse model for understanding human iron metabolic disorders.