Aquaporins: important but elusive drug targets

Nat Rev Drug Discov. 2014 Apr;13(4):259-77. doi: 10.1038/nrd4226. Epub 2014 Mar 14.


The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aquaporins / metabolism*
  • Biological Transport
  • Cell Membrane / metabolism
  • Drug Design*
  • Humans
  • Mice
  • Mice, Knockout
  • Molecular Targeted Therapy*
  • Osmosis
  • Water / metabolism


  • Aquaporins
  • Water