In this invited article, we review and discuss the evidence and recently published studies supporting our hypothesis that intratubular Ang II and AT1 (AT1a) receptors in the proximal tubules of the kidney are required for maintaining basal blood pressure homeostasis and for the development of Ang II-induced hypertension and renal injury, and that deletion of AT1a receptors selectively in the proximal tubules will attenuate Ang II-dependent hypertension and renal injury. The gene discussed is AGT; the disease is hypertensive disorder.