SLC48A1 encodes a heme transporter essential for iron homeostasis in mammals. The protein mediates transport of heme from endosomal and lysosomal compartments into the cytoplasm, facilitating heme-iron recycling during erythrophagocytosis in reticuloendothelial macrophages 1. This recycling pathway is quantitatively significant—SLC48A1-mediated iron recovery is equivalent to at least 10 parts per million of dietary iron 2. Beyond macrophages, SLC48A1 is highly expressed in oligodendrocytes of the central nervous system, where it localizes to myelin sheaths and supports iron availability for myelin proteolipid biosynthesis 3. In the absence of functional SLC48A1, heme accumulates in lysosomes and is tolerated through crystallization into hemozoin, a mechanism that requires intact heme degradation pathways; deficiency in both SLC48A1 and HMOX1 is perinatally lethal 4. SLC48A1 mutations contribute to adult-onset autosomal recessive sideroblastic anemia and impaired erythroid maturation. Elevated SLC48A1 expression in lung adenocarcinoma and squamous cell carcinoma supports tumor oxidative phosphorylation and proliferation, and heme sequestration targeting SLC48A1-mediated uptake suppresses tumor progression in preclinical models 5. The gene is a transcriptional target of the NRF2 antioxidant response pathway 6, linking heme metabolism to oxidative stress responses.