Disease-specific manifestations of ET-1 dysregulation include impaired Aβ clearance and endothelial dysfunction in AD, ischemic penumbral expansion and inverse NVC in stroke/subarachnoid hemorrhage, cortical spreading depolarization in migraine, hyperexcitability in epilepsy, and microvascular degeneration with mitochondrial failure in CSVD and TBI. The gene discussed is EDN1; the disease is migraine disorder.