Glycogen synthase kinase 3beta (GSK-3beta) was subsequently shown to function in a wide range of cellular processes. GSK-3beta is a multifunctional serine/threonine kinase which performs a role in several signaling pathways including Wnt signal transduction. Recently, the activity of membrane-localized GSK-3beta has been shown to be crucial for initiation of Wnt cascade. In our study, the membrane localization of GSK-3beta was found on the apical membrane of normal epithelium, where co-localized and directly bound with MUC1. In colorectal cancer, depolarized cells showed the aberrant distribution of GSK-3beta on the cellular membrane with beta-catenin nuclear accumulation. The aberrant distribution of the membrane-localized GSK-3beta may contribute to the development of colorectal cancer.