In studying the physiology and diseases of a given organ, the identification of the major differentiation products of that particular organ is a crucially important step. Detailed knowledge on the structure and function of these molecules, which are frequently accumulated in large quantities during cellular differentiation, help elucidate the molecular basis of important physiological processes, such as muscle contraction. Mutations of many of the tissue-specific products have been found to be the underlying causes for many organ-restricted diseases. The availability of promoters of some of these tissue-specific genes enables one to drive various transgenes including mutated differentiation products, specific oncogenes, dominant negative mutants of various receptors, to express uniquely in the target organ. The resultant pathology and abnormal physiology can yield great insights on the functions of the differentiation products per se and various test molecules, as well as the mechanisms of many human diseases. It is in this context that the recent identification of uroplakins as the major differentiation products of mammalian urothelium is important, as this has made it possible to employ many approaches, that have proven to be fruitful in other organ systems, for elucidating the biochemical mechanisms of urothelial growth and differentiation. In this paper, we will discuss what has been learned recently about the uroplakin molecules and their possible role in urothelial differentiation.