While Nrf2 signaling is often suppressed globally in COPD lungs, its dysfunction in macrophages may paradoxically promote ferritinophagy-mediated iron retention through nuclear receptor coactivator 4 (NCOA4), overwhelming ferroprotein (FPN)-mediated iron export and unintentionally fueling ferroptosis. This evidence concerns the gene NFE2L2 and chronic obstructive pulmonary disease.