English: Iron crosses the blood–brain barrier (BBB) either by:

• The transcytosis pathway, where the complex “diferric Fe3+-transferrin-transferrin receptor 1 (TfR1)” undergoes endocytosis and exocytosis from the luminal pole to the cerebral extracellular matrix (ECM) and interstitial fluid.

• The facilitated transporter pathway, where endothelial cells internalize the complex “diferric Fe3+-transferrin-transferrin receptor 1 (TfR1)” in endosome, reduce ferric Fe3+ ion to ferrous Fe2+ ion by STEAP3 enzyme and then Fe2+ ion crosses the endosomal membrane thanks to DMT1. Fer²+ is then exported to the extracellular matrix (ECM) and interstitial fluid, via ferroportin coupled with ceruloplasmin (Note that transferrin is not only a plasmatic protein and choroid plexuses can secrete it).