ATP6AP2 (also known as the (pro)renin receptor) is a type I transmembrane protein that can be cleaved into two fragments in the Golgi apparatus. While in Drosophila ATP6AP2 functions in the planar cell polarity (PCP) pathway, recent human genetic studies have suggested that ATP6AP2 could participate in the assembly of the V-ATPase in the endoplasmic reticulum (ER). The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin-angiotensin systems, but also interacts with Wnt pathways and vacuolar H(+) -ATPase (V-ATPase) during organogenesis. ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system.