Water is essential for cells, yet lipid membranes normally resist water flow. By analyzing membrane proteins from red blood cells and kidneys, Agre isolated in 1992 a protein that enables rapid, selective water transport. He named it “aquaporin” and used gene-transfected cells and liposomes in osmotic assays, showing a dramatic increase in water permeability. This discovery advanced our understanding of water-balance regulation and diseases such as diabetes insipidus. Moreover, aquaporins are widespread in plants and bacteria, highlighting a fundamental evolutionary solution for water management.

AQP1, identified by Agre, consists of six trans-membrane helices and two conserved NPA motifs; a positively charged pocket near the channel center blocks proton hopping, ensuring selectivity. X-ray crystallography later revealed a single-file chain of water molecules that flip their dipoles while moving through the channel. In kidney collecting ducts, vasopressin triggers vesicular translocation of AQP2 to the plasma membrane, regulating water reabsorption. In plants, tonoplast aquaporins support turgor maintenance and salt tolerance, driving agricultural research. Development of aquaporin inhibitors and engineered channels promises therapeutic strategies for brain edema and novel membrane-separation technologies.

The AQP family belongs to the Major Intrinsic Protein superfamily, with twelve human members (AQP0–AQP12). A remarkable flux of ~10^9 H₂O molecules s⁻¹ surpasses simple diffusion owing to hydrophobic wall residues and electrostatic alignment near the NPA motifs. Molecular-dynamics simulations visualize single-file water chains constrained to block Grotthuss proton relay, consistent with experimental pKa-shift analyses. Cryo-EM structures in native lipid environments suggest raft-dependent oligomerization affects gating dynamics. Recently, autoantibodies against the AQP4 isoform were identified as the principal antigen in neuromyelitis optica, bridging channel biology with immunopathology.