The (Pro) renin receptor ((P) RR) has attracted considerable interest from cardiovascular researchers, since its discovery in 2002 by Nguyen et al. 1 It filled a gap in the understanding of the renin-angiotensin system (RAS) by providing the basis of renin uptake into organs such as the heart, where this enzyme is normally not generated. Furthermore, it ended the concept of prorenin being an inactive precursor of renin by showing that binding of prorenin to (P) RR leads to its activation via a non-proteolytic mechanism and to the local generation of angiotensins. Surprisingly however, the binding also elicited additionally an angiotensinindependent signalling in (P) RR expressing cells. Altogether,(P) RR could explain the elusive mechanisms of action of prorenin involved in tissue damage which was found to be associated with states of high circulating prorenin such as transgenic overproduction of the protein2 or diabetes mellitus. 3 The interest in (P) RR was further fuelled by the findings of Ichihara et al. that a peptide designed to interfere with the binding of prorenin to (P) RR can ameliorate or even completely block tissue damage induced by diabetes or hypertension in mice and rats. 4-6 Things got even more heated up by the parallel development of novel drugs targeting the RAS, the renin inhibitors. Their potential interaction with the binding of prorenin or renin to (P) RR became extremely interesting since it would implicate an additional therapeutic benefit of these drugs.

In all this hype, it got forgotten that (P) RR had been described long before its characterisation as being a (pro) renin binding protein. In 1998, Ludwig et al. 7 had found the C-terminal part of the protein being associated with the vacuolar H+-ATPase in chromaffin cells of the adrenal medulla, and the second name of the protein is