Transepithelial transport of acid, base, and electrolytes, and the transport of calcium across cellular membranes is of critical importance in homeostatic processes that are disturbed in a number of human disease states, including heart disease, hypertension, kidney diseases, and gastrointestinal disorders. To understand the physiological functions of epithelial ion transporters and calcium pumps in both health and disease, we are developing mouse models in which the corresponding genes have been disrupted. So far, we have developed mouse models for a number of Na/H exchangers, H,K-ATPases, Na-coupled electrolyte transporters, channels, and calcium pumps. Our analyses of these mice, using molecular, cellular, and physiological techniques, are yielding important new insights into the physiological functions of these ion transporters in the living animal. Support for trainees is available from a Training Grant in Cardiovascular Research. This training program can be viewed at the following web site: CV Training Grant