Epithelial cells mediate the unidirectional movement of selective compounds from one biological compartment to another. This is accomplished by having biochemically, structurally, and functionally distinctive apical and basolateral surface membrane domains separated by the cells’ junctional complex. Derangement of this highly ordered situation can result in cell injury, dysfunction, and even death. For renal epithelial cells, both ischemia and polycystic kidney disease are known to result in a loss of surface membrane polarity. In both disease processes, this in turn plays an important role in cell and organ dysfunction.