Since the discovery of the (pro)renin receptor (PRR) much effort was made to establish its role in pathology, hoping to optimize the blockade of the renin-angiotensin system with a PRR blocker. In spite of a positive correlation between a polymorphism of the PRR gene called ATP6AP2 and higher blood pressure in Japanese and Caucasian subjects, experimental models failed to clearly establish a link between PRR, hypertension and organ damage. Because complete ablation of the PRR/ATP6AP led to embryonic lethality in mice, contrary to all other components of the RAS, more essential cellular function of PRR were suspected. These functions are related to the vacuolar H+-ATPase (V-ATPase), the ATP-dependent proton pump that acidifies intracellular vesicles lysosome, endosomes and to the Wnt signalling pathways. Indeed, conditional knock-out of PRR in cardiomyocytes and podocytes revealed an essential role of PRR in the assembly and the function of the V-ATPase, leading to impaired vesicles acidification and endocytosis, increased autophagy, cell apoptosis and rapid death of the animal. Moreover, PRR is involved in the Wnt/beta-catenin and Wnt/Planar Cell Polarity signalling pathways that are absolutely critical during embryonic development. It is important to stress that the functions of PRR in the V-ATPase and in Wnt signalling are totally independent of renin and prorenin. PRR is cleaved intracellularly by furin to generate a soluble form (sPRR) actively secreted in plasma and in urine. sPRR is able to bind renin and prorenin and to activate prorenin. Our results of sPRR determination in plasma show that it is not correlated with age, gender, plasma renin or prorenin. Altogether, these results indicate that PRR has much broader functions than binding renin and prorenin and they question the role of PRR in patho-physiological states related to the activation of the renin angiotensin system.