Fig. 1

ATRAP and the Skin Renin-Angiotensin System: From Mechanism to Therapeutic Modulation of Hypertension. This schematic illustrates the proposed mechanism by which ATRAP (Angiotensin II type 1 receptor-associated protein) regulates cutaneous RAS activity and contributes to systemic blood pressure (BP) regulation. Under physiological conditions, ATRAP promotes internalization of the angiotensin II type 1 receptor (AT1R) in keratinocytes, thereby attenuating Ang II–mediated signaling and limiting local RAS activation. In keratinocyte-specific ATRAP deficiency, AT1R internalization is impaired, leading to sustained Ang II signaling, increased expression of angiotensinogen and Ang II in the skin, and enhanced vasoconstriction in the cutaneous vascular bed. This vasoconstriction reduces cutaneous blood flow and transepidermal water loss (TEWL), thereby contributing to systemic BP elevation. The model also highlights the therapeutic potential of transdermal ARBs, Rho kinase (ROCK) inhibitors, and skin-warming therapy, which can normalize vascular tone and mitigate Ang II-induced hypertensive responses. These findings position the skin RAS as a novel and accessible target for antihypertensive intervention, particularly in treatment-resistant hypertension