SLC40A1 (ferroportin) is the sole mammalian cellular iron exporter, transporting ferrous iron (Fe2+) from the cytoplasm to the extracellular space 1. It is essential for systemic iron homeostasis, mediating iron efflux from intestinal enterocytes (dietary iron absorption), splenic and hepatic macrophages (iron recycling), and hepatocytes (iron storage release) 1. SLC40A1 is the key functional target of hepcidin, the iron-regulatory hormone; elevated serum hepcidin causes SLC40A1 degradation, reducing iron export during iron excess, while decreased hepcidin during iron deficiency permits ferroportin-mediated iron delivery to plasma 1. Dysregulated SLC40A1 expression impairs cellular iron metabolism, leading to intracellular iron accumulation and ferroptosis 2. Mutations in SLC40A1 that disrupt hepcidin binding cause ferroportin disease, an autosomal dominant hemochromatosis characterized by cellular iron retention in reticuloendothelial cells with high serum ferritin and low-normal transferrin saturation 3. SLC40A1 dysfunction in tumor-associated macrophages correlates with poor prognosis in hepatocellular carcinoma 4. These findings establish SLC40A1 as a critical iron metabolism regulator with implications for both physiological homeostasis and disease pathogenesis.