Aquaporin-5 (AQP5)

Aquaporin-5 (AQP5) is a small integral membrane protein (265 amino acids, ≈28 kDa) that forms water-selective channels within cell membranes[2][5][6]. It is one of the major aquaporins in mammals, predominantly expressed in secretory glands (such as salivary, lacrimal, and sweat glands), lung airway epithelium, stomach, pancreas, and other tissues[6][9]. AQP5 assembles as a homotetramer in the membrane, with each monomer containing six transmembrane α-helices and a characteristic NPA (asparagine–proline–alanine) motif forming the water-selective pore[1][2][3][5][6]. Its physiological function is the rapid and selective transport of water across epithelial cell membranes, enabling high-capacity fluid secretion in saliva, tears, and pulmonary secretions[2][3][9]. AQP5 expression and membrane localization is regulated by phosphorylation and trafficking, which can be altered in various diseases. Abnormal AQP5 activity or localization is implicated in numerous pathological states, including several cancer types (where it can act as a biomarker of aggressiveness and possibly promote tumor cell survival and migration), cystic fibrosis-associated lung disease, and Sjögren’s syndrome[7][9]. No clinically approved drugs currently target AQP5 directly, though it remains a potential therapeutic target in cancer and glandular disorders.

Other names

Aquaporin 5AQP-5Water channel protein AQP-5

Modulation of water channel activity (e.g., via channel blockade or by altering membrane trafficking). Experimental small-molecule AQP inhibitors target the water channel pore or block trafficking to the membrane[7].