(A) Non-BBB containing lung endothelial cells do not express Mfsd2a, display low levels of DHA, and display high levels of transcytotic caveolae vesicles, characterized by the presence of Cav-1 coat protein (purple). (B) BBB-containing brain endothelial cells express Mfsd2a (green). Mfsd2a acts as a lipid flippase, transporting phospholipids, including DHA-containing species (orange), from the outer to inner plasma membrane leaflet. The increased levels of DHA, and presumably other lipid changes, alter the plasma membrane composition such that caveolae vesicles are unable to form and act as transcytotic carriers. Thus, brain endothelial cells display low levels of caveolae vesicles. This suppression of caveolae formation and trafficking subsequently ensures BBB integrity under normal conditions.