In terms of one current conceptual model (see Figure 1 in [280]) there are two possible fates of transferrin and iron after endocytosis. In the first fate, holo-transferrin is exocytosed across the abluminal membrane as in the original hypothesis. However the current consensus is that relatively little holo-transferrin is in fact exocytosed on the brain side [262, 279–282, 626–628]. In the second fate, dissociation of the holo-transferrin occurs within endosomes in the endothelial cells with the iron being transported across the abluminal membrane by ferroportin. In this option, one that is preferred by Simpson et al. [280], the iron-free apo-transferrin is exocytosed, part across the abluminal membrane accounting for the observed transfer of transferrin from blood to brain but primarily across the luminal membrane back to blood. This model allows the possibility that transcytosis of apo-transferrin can occur from brain to blood. The site of dissociation of the iron from the holo-transferrin inside the endothelial cell layer and the intervening steps are still under active investigation [281, 282]).