Cancer patients have been characterized by decreased iron availability in mitochondria, and iron supplementation was sufficient to preserve muscle function.[45] As reported, muscles from old mice had increased iron levels, which were associated with increased susceptibility to ischemia‐reperfusion injury and impaired muscle regeneration.[46] Herein, our data demonstrated that Huwe1 deficiency in the skeletal muscle leads to iron overload through downregulating Fpn, which exports iron from cells to plasma. This evidence concerns the gene HUWE1 and cancer.