Proposed functions of extracellular microvesicles (EMVs) at the blood–brain barrier. EMVs ‘shed’ from the luminal membranes of BEC into the circulation contain unique molecules (as indicated by star) that potentially can be used as CNS-specific markers. Ligand binding to receptor-mediated transcytosis (RMT) receptor on the luminal surface leads to receptor-mediated endocytosis. The ligand/receptor complex is then sorted through the endocytic pathway into multivesicular bodies (MVBs) and is externalized on the abluminal side in abluminal EMVs. The EMVs can communicate with cells in the brain, including neurons and astrocytes through protein-protein surface interactions followed by transfer of RNA/protein molecules. A similar process may occur in the opposite direction, resulting in RMT receptor recycling, or ‘transfer’ of parenchymal exosomes into the systemic circulation.