On the endothelial side, we recently reported that retro-orbital application of a water-soluble analog of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), which is an essential cofactor for Kir2.1 channels (43), restores Kir2.1 channel-mediated functional hyperemia in mouse models of both CADASIL (12) and AD (14). Here, KCNJ2 is linked to Alzheimer disease.