The hedgehog signaling pathway first described in Drosophila and conserved in vertebrates, has an important role in early embryonic patterning as well as continued control of cell growth and differentiation. Mutations in patched, the hedgehog receptor, cause Gorlin syndrome. Patched also functions as a tumor suppressor in sporadic basal cell carcinoma of the skin and inactivation of patched appears to be a necessary if not sufficient step in the pathogenesis of most of these tumors. Patched is a large membrane bound protein with little homology to known proteins or protein motifs. Mutational analysis of Gorlin patients and related tumors suggest possible functional domains. Several missense mutations have been described that tend to cluster in specific regions. Since the patched protein is large and tends to be difficult to study by conventional means, a patched-green fluorescent protein construct was developed and transfected into cell culture. The advantage of this technique is that the protein of interest can be studied live and in real time under a confocal microscope and the tag does not appear to interfere with normal movement and function. Baseline studies for the patched protein have been determined. The purpose of this study is to evaluate the effects of missense mutations described in tumors and patients on the normal localization and trafficking of the patched protein. Information obtained will enhance understanding of the role of patched in carcinogenesis. Alternative methods of treatment or prevention of basal cell carcinoma of the skin may be suggested by these studies.