Aquaporin-5 (AQP5) (AQP5)

Aquaporin-5 (AQP5) is a member of the aquaporin family of integral membrane proteins that function as water-selective channels. It is predominantly expressed in the apical plasma membranes of secretory cells in the salivary, lacrimal, and sweat glands, as well as in the type I pneumocytes of the lung [1, 2]. The physiological function of AQP5 is critically dependent on its subcellular distribution; it translocates from intracellular vesicles to the plasma membrane (trafficking) in response to stimuli such as muscarinic receptor activation [3]. Conversely, it is internalized via endocytosis to terminate water transport, a process regulated by phosphorylation and protein-protein interactions [4]. In Sjögren's syndrome, a defect in this trafficking mechanism leads to the mislocalization of AQP5, contributing to the hallmark symptoms of dry mouth and dry eyes [5]. Furthermore, AQP5 overexpression has been implicated in the progression and metastasis of several cancers by promoting cell proliferation and migration [6]. While direct pharmacological inhibitors or activators of AQP5 are still in development, current therapies like cevimeline and pilocarpine indirectly target the AQP5 trafficking pathway by acting as agonists for the M3 muscarinic acetylcholine receptor [7]. Understanding the regulation of AQP5 trafficking remains a key area for developing novel treatments for fluid distribution disorders and certain malignancies.

Other names

AQP-5Water channel protein AQP5

Facilitates transmembrane water movement along osmotic gradients. Its activity is regulated by translocation from intracellular storage vesicles to the apical plasma membrane (trafficking) and subsequent internalization (endocytosis), primarily driven by muscarinic and adrenergic signaling pathways.