In the intestinal tract, transmucosal ion and fluid movement is dominated by the action of a defined set of ion transport proteins. CFTR, in conjunction with members of the SLC26 anion exchanger family, mediates electrogenic Cl^- and HCO₃^­ secretion. NHE3, coupled to one or several of the SLC26 isoforms, mediates electroneutral NaCl absorption. Nutrient-coupled electrolyte transport mediates the bulk of postprandial fluid absorption, and in the distal colon, the epithelial Na⁺ channel ENaC enables a near complete removal of salt from the stool. Major breakstones in the recent past include the cloning of new intestinal ion transporters, the evolvement of new concepts for the regulation of electrolyte transport through the PDZ-domain-adapter-mediated formation of multiprotein signaling complexes, and the understanding that nutrient and ion transporters appear to work in a coordinated fashion. One example is the cloning of the intestinal members of the SLC26 gene family of anion transporters. Current investigations focus on finding out what physiological roles the different members of this gene family have in the different segments of the GI tract.

Ion transporters appear to be regulated in multiprotein complex of transport proteins, PDZ adapter proteins, anchoring proteins, the cytoskeleton, and the involved protein kinases. For the regulation of intestinal electrolyte transport, the members of the so-called NHERF family of PDZ-adapters play a pivotal role. Recently, first results in NHERF knockout mice suggest a more cell-type and signal-specific role of these adapter proteins than anticipated. This opens the potential for drug development targeted to PDZ domain interactions, which has potential in the treatment of diarrheal diseases, cystic fibrosis and other ion transport dysfunctions.