The (Pro)Renin Receptor, PRR, was identified as a component of the renin-angiotensin system but studies have revealed that it is a multifunctional molecule. The unique gene called ATP6ap2/PRR located on the X chromosome encodes a unique splice variant. However the protein undergoes intracellular processing generating a soluble form of PRR that can be measured in plasma and a membrane-cytoplasmic form associated with the vacuolar proton-ATPase. It was initially shown that PRR-bound renin and prorenin, increasing their enzymatic activity and activating intracellular signaling upregulating the expression of profibrotic proteins. Therefore most studies focused on the role of PRR in hypertension, cardiovascular and renal diseases, organ damage trying to identify PRR as a therapeutic target to optimize RAS blockade. Recent data have now confirmed that renin bound to PRR more efficiently catalyzes the conversion of angiotensinogen to angiotensin, based on crystal structure analysis, and that PRR is linked to blood pressure and plasma aldosterone levels, based on gene polymorphism studies. However, specific PRR deletion in cardiomyocytes and in podocytes draw our attention to a functional link between PRR and the vacuolar proton-ATPase and, in Xenopus and in Drosophila, ubiquitous or tissue-specific knock-down is responsible for embryonic lethality and severe epithelia abnormalities attributed to a defect in Wnt signaling pathways, independently of (pro)renin. The use of PRR conditional deletion to study the effect of tissue-specific ablation in adult and in embryo will clearly help deciphering the pathophysiological roles of PRR in development and in diseases.