aquaporin4

Aquaporin-4 (AQP4) is a water channel protein of the aquaporin family that forms tetramers in the plasma membrane and facilitates rapid, regulated water movement across cell membranes. In humans, the AQP4 gene is located on chromosome 18 and encodes the predominant water channel in the central nervous system.

Expression is highest in astrocyte endfeet that ensheath cerebral blood vessels and border the ventricles and meninges. AQP4 forms orthogonal arrays of particles (OAPs) in the plasma membrane, an organization influenced by the relative abundance of two major N-terminal isoforms, M1 and M23; the M23 form favors larger OAPs, while M1 can limit assembly.

Functionally, AQP4 enables bidirectional water transport in response to osmotic gradients, contributing to brain water homeostasis. It is implicated in the glymphatic system, facilitating exchange between cerebrospinal fluid and interstitial fluid and aiding clearance of metabolic waste. It also participates in edema development and resolution after brain injury or stroke.

Clinical significance centers on autoimmunity: autoantibodies against AQP4 (NMO-IgG) target the protein and cause astrocyte injury and demyelination, defining neuromyelitis optica spectrum disorders. Detection of AQP4 antibodies is used diagnostically. Genetic mutations in AQP4 are rare; most disease associations relate to autoimmune processes rather than congenital deficiency. Therapeutic approaches for affected individuals often involve immunosuppression or plasma exchange.