In mice not treated with ALA, alterations in Mfrn1 were not associated with signs of protoporphyria, possibly because of the Irp1-mediated suppression of Alas2—in fact, Mfrn1-deficient mice start to develop protoporphyrin accumulation when the interaction between Alas2 and Irp1 is impaired [59]. The gene discussed is ACO1; the disease is erythropoietic protoporphyria.