Physiology of the (pro)renin receptor: Wnt of change?

The (pro)renin receptor is a protein that binds prorenin and renin in tissues, leading to their activation and, at the same time, to the initiation of intracellular signaling. The activation of local renin–angiotensin systems may play an important role in tissue damage induced by cardiovascular diseases and diabetes. However, (pro)renin receptor is also called ATP6ap2 because it has been shown to be associated with vacuolar H+-ATPase involvement in vesicular acidification and signaling in cells. Notably, lack of the protein in vertebrates leads to developmental alterations and early embryonic lethality probably as a result of the recently discovered role of the (pro)renin receptor and the vacuolar H+-ATPase in Wnt signaling. This review summarizes the current findings about these two functions of (pro)renin receptor/ATP6ap2 pointing out the possible links between both.