Aquaporin water channels: distribution, physiology, pathophysiology, and relevance as therapeutic targets

Abstract Aquaporins (AQPs) represent a class of integral membrane proteins that function as selective water channels, facilitating the transit of water molecules across biological membranes. Under specific conditions, these proteins may also mediate the permeation of small solutes, including glycerol, hydrogen peroxide, urea, carbon dioxide, and ammonia. Investigations into AQPs have unveiled distinctive structural attributes and functional properties. Evidence indicates that AQPs are broadly distributed across diverse tissues and organ systems in humans, contributing to essential physiological processes. An expanding body of literature highlights the involvement of AQPs in disease pathogenesis and progression, particularly in cellular behaviors such as proliferation and motility, pulmonary gas exchange, and the modulation of non-canonical signaling pathways. This review comprehensively outlines the tissue-specific and subcellular distribution profiles, physiological roles, and regulatory mechanisms associated with AQPs. It further characterizes the alterations in AQP functionality under pathological states, delineates their involvement and mechanistic contributions to multisystem disorders, and provides an overview of therapeutic strategies targeting AQPs, along with their translational prospects. In addition, key gaps in current knowledge are identified, and pivotal research directions, such as tissue-specific modulation and the design of targeted inhibitors and activators, are proposed to advance the translational application of AQPs as diagnostic and therapeutic targets.