Vacuolar H-ATPase (V-ATPase) is a multisubunit protein complex which, along with its accessory proteins, resides in almost every eukaryotic cell. It acts as a proton pump and as such is responsible for regulating pH in lysosomes, endosomes, and the extracellular space. Moreover, V-ATPase has been implicated in receptor-mediated signaling. Although numerous studies have explored the role of V-ATPase in cancer, osteoporosis, and neurodegenerative diseases, research on its involvement in vascular disease remains limited. Vascular diseases pose significant challenges to human health. This review aimed to shed light on the role of V-ATPase in hypertension and atherosclerosis. Furthermore, given that vascular complications are major complications of diabetes, this review also discusses the pathways through which V-ATPase may contribute to such complications. Beginning with an overview of the structure and function of V-ATPase in hypertension, atherosclerosis, and diabetes, this review ends by exploring the pharmacological potential of targeting V-ATPase.
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