(Pro)renin receptor ((P)RR) is a specific receptor for renin and prorenin, and is a new component of the renin angiotensin system (RAS) (1, 2). When bound to prorenin, (P)RR activates the angiotensin I-generating activity of prorenin in the absence of cleavage of the prosegment. Moreover, binding of (pro)renin to (P)RR directly activates MAPK ERK1/2 independently of the RAS. The gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory protein 2), and (P)RR was initially found as a truncated form co-purifying with V-ATPase (vacuolar H+-ATPase). The association of (P)RR and V-ATPase has been shown to be functional and essential for the survival of certain cells. Furthermore, (P)RR is involved in the Wnt/β-catenin pathway. It is therefore likely that (P)RR has an important role in the physiology and pathophysiology of cell proliferation. The aim of the present study is therefore to clarify the role of (P)RR in cell proliferation. Cultured human breast carcinoma cell lines were used in the present study. Western blot analysis (3) showed expression of (P)RR protein in all 4 breast carcinoma cell lines examined; MCF-7, T47D, SK-BR-3 and MDA-MB-231. Transfection of (P)RR specific small interference RNA decreased cell proliferations in breast carcinoma cell lines. Treatment with angiotensin II did not stimulate cell proliferation or phosphorylation of ERK1/2 in cultured breast carcinoma cells, suggesting that the stimulatory effect of (P)RR on cell proliferation occurred independently of the RAS. By contrast, treatment with prorenin increased phosphorylation of ERK1/2 in these cells. Treatment of bafilomycin A1, an inhibitor of V-ATPase, greatly inhibited cell proliferation of human breast carcinoma cells. These findings suggest that (P)RR stimulates cell proliferation independently of the RAS, possibly via the stimulation of ERK1/2 and/or the function of V-ATPase. The present study has raised the possibility that (P)RR is a novel target for the development of the new therapies, not only in cardiovascular, renal diseases including diabetic nephropathy (4), but also in proliferative diseases including cancers.