We have found that in CADASIL, the most common genetic small vessel disease of the brain, this Kir2.1-mediated signaling mechanism is abrogated in capillary ECs but is fully intact in arteriolar ECs (12), whereas it is crippled in both arteriolar and capillary ECs in the context of hypertension, a major driver of more common sporadic small vessel disease of the brain (13). This evidence concerns the gene KCNJ2 and hypertensive disorder.