The absence or dysfunction of key proteins in these regulatory pathways and their receptors can cause dysregulation of nonheme iron uptake, leading to serious consequences.21 For instance, systemic iron is bound primarily to the TF and cellular iron uptake is mediated by TF and its receptor TFR1.22 Systemic TF knockout mice die within one day of birth.20 Mice lacking TFR1 develop fatal cardiomyopathy with failed oxidative phosphorylation and impaired mitophagy, but iron supplementation prevents these complications.38 Here, TFRC is linked to cardiomyopathy.