Vacuolar-type H+-ATPase (V-ATPase) is a multisubunit enzyme responsible for acidification of eukaryotic intracellular organelles. V-ATPases pump protons against an electrochemical gradient, thereby synthesizing ATP. A peripheral V1 domain, which is responsible for ATP hydrolysis, and an integral V0 domain, which is responsible for proton translocation, compose the V-ATPase. Nine subunits (A–H) make up the V1 domain and five subunits (a, d, c, c' and c") make up the V0 domain. ATP6AP1 (ATPase, H+ transporting, lysosomal accessory protein 1), also known as 16A, CF2, Ac45, XAP3, ATP6S1, VATPS1 (vacuolar ATP synthase S1 accessory protein) or ATP6IP1, is a type I transmembrane, V-ATPase accessory protein that is predominantly expressed in endocrine and neuronal cells. ATP6AP1 is responsible for targeting the V-ATPase enzyme to specialized complex vacuolar systems. Via its cytoplasmic tail, ATP6AP1 interacts with subunits of the V0 domain. The disruption of this interaction in osteoclasts results in impaired bone resorption, suggesting an important role for ATP6AP1 in proper osteoclastic bone resorption.