Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system (By similarity). May mediate renin-dependent cellular responses by activating ERK1 and ERK2 (By similarity). By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, may also play a role in the renin-angiotensin system (RAS) (By similarity). Through its function in V-type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signaling pathways important for proper brain development, synapse morphology and synaptic transmission (PubMed:26376863, PubMed:29127204, PubMed:30985297). Interacts with renin. Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump. Interacts (via N-terminus) with ATP6AP1 (via N-terminus). Interacts with ATP6V0D1; ATP6V0D1 is a V-ATPase complex subunit and the interaction promotes V-ATPase complex assembly. Interacts with TMEM9; TMEM9 is a V-ATPase assembly regulator and the interaction induces the interaction with ATP6V0D1. Interacts with VMA21 (via N-terminus); VMA21 is a V-ATPase accessory component. Expressed in glutamatergic and GABAergic neurons with highest levels in the cortex, the hippocampus, the medial habenular nucleus, the cerebellum, the medulla and the olfactory bulb (at protein level). Expressed at 12 dpc throughout the developing cortex with notable apical enrichment in radial glial cells (RGCs) along the ventricular surface. Phosphorylated. Proteolytically cleaved by a furin-like convertase in the trans-Golgi network to generate N- and C-terminal fragments. Conditional knockout mice lacking Atp6ap2 in glutamatergic neurons display increased spontaneous locomotor activity and altered fear memory; show abnormal number and morphology of synapses, presynaptic transmission and autophagy defects that lead to axonal and neuronal degeneration in the cortex and hippocampus (PubMed:26376863). Conditional knockout mice lacking Atp6ap2 in the liver display liver damage, hypoglycosylation of serum proteins and autophagy defects (PubMed:29127204, PubMed:26376863). Conditional knockout mice lacking Atp6ap2 in cortical neurons die around 4 weeks of age (PubMed:30985297). It is associated with a flattened forehead and deficits in neural cell generation and/or survival compared to controls. Mutant embryonic cortex shows reduced proliferation of progenitor neural cells with premature exit of the cell cycle, premature differentiation, and apoptosis. There is also evidence of lysosomal dysfunction, impaired protein degradation in autophagolysosomes, and dysregulation of the mTOR kinase pathway.