The (pro)renin receptor: a new addition to the renin-angiotensin system?

The renin-angiotensin system is still incompletely understood. In particular, the function of prorenin, the inactive precursor of renin, is unknown. Yet, prorenin levels are >10-fold higher than renin levels, and prorenin increases even further in subjects with diabetes mellitus displaying microvascular complications. The recent discovery of a (pro)renin binding receptor may shed light on the role of prorenin. This review discusses the possibility that prorenin binding to this receptor results in prorenin activation, thereby allowing angiotensin generation, and that prorenin simultaneously acts as an agonist of this receptor, inducing angiotensin-independent effects. Transgenic animals overexpressing the receptor, as well as a receptor antagonist are now available, and future studies should reveal to what degree this concept is applicable to humans as well.