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In the brain, dysregulation of the ET system contributes to cerebral hypoperfusion, impaired neurovascular coupling, blood\u2013brain-barrier disruption, and neuroinflammation. In this review, we synthesize evidence supporting ET system signaling as a mechanistic and translational bridge between renal and cerebral microvascular dysfunction and discuss how shared cardiometabolic and autoimmune risk factors may amplify ET signaling, thereby worsening kidney\u2013brain outcomes. 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