Signal transduction in epithelial cells adds another level of complexity to the signaling that occurs in symmetrical cells, in the form of the need to coordinate and keep separate signals at the apical and basolateral membranes. Regulation by protein kinases of ileal NaCl absorption and its component brush-border Na+/H+ exchanger are used as an example of how signaling in epithelial cells must deal with spatial localization of signals, protein-protein interactions, signaling molecules, and the involvement of the transport protein being regulated in collecting and focusing the signals generated at the receptor and beyond.