Forms a water-specific channel (PubMed:8660998, PubMed:9276712, PubMed:18286643). Plays an important role in brain water homeostasis and in glymphatic solute transport (PubMed:22896675, PubMed:27751903, PubMed:30561329, PubMed:30557661). Required for a normal rate of water exchange across the blood brain interface (PubMed:30557661). Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP (PubMed:22896675, PubMed:27751903, PubMed:30561329). Plays a redundant role in urinary water homeostasis and urinary concentrating ability (PubMed:9276712). Homotetramer. The tetramers can form oligomeric arrays in membranes. The size of the oligomers differs between tissues and is smaller in skeletal muscle than in brain. Interaction between AQP4 oligomeric arrays in close-by cells can contribute to cell-cell adhesion (By similarity). Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1 (By similarity). Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane (By similarity). Detected on brain astrocyte processes and astrocyte endfeet close to capillaries (PubMed:22896675). Detected in brain cortex, especially around cortical blood vessels, and subjacent to pia, with lower levels in parenchymal membranes (PubMed:27751903). Detected in ependymal and astroglial cells in brain (PubMed:8660998, PubMed:9276712, PubMed:22896675, PubMed:27751903). Detected in supporting Hensen's cells, inner sulcus cells and Claudius cells in the inner ear (PubMed:11406631). Detected in skeletal muscle (PubMed:29055082). Detected in gastric parietal cells (PubMed:10915655). Detected in principal cells in collecting ducts in kidney medulla (at protein level) (PubMed:9276712, PubMed:16641094). Detected in brain, heart and skeletal muscle (PubMed:8660998). Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Phosphorylation by PKC at Ser-180 reduces conductance by 50% (By similarity). Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40%; this increase is not due to increased presence at the cell membrane (PubMed:18286643). Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not palmitoylated. Mice are born at the expected Mendelian rate and display no obvious phenotype (PubMed:9276712, PubMed:10915655). They have normal urine osmolality under standard conditions, but display reduced urine osmolality after 36 hour water deprivation (PubMed:9276712). Adult mice display incereased brain water content (PubMed:27751903). Mutant mice display a reduced rate of water flux across the blood brain interface (PubMed:30557661). Fluid transport from the brain paravascular space into the surrounding interstitium is abolished. Besides, mice display strongly reduced solute clearance from the brain interstitium (PubMed:22896675). Mice display reduced cerebrospinal fluid influx into the brain, and reduced brain solute transport via the cerebrospinal fluid from the cisterna to the brain parenchyma (PubMed:22896675, PubMed:30561329). The organ of Corti in the inner ear appears morphologically normal, but mice have considerably impaired hearing at an age of 4 to 5 weeks (PubMed:11406631). Mice display unchanged gastric acid secretion (PubMed:10915655). Belongs to the MIP/aquaporin (TC 1.A.8) family.