Telencephalin is a neural glycoprotein that reduces apoptosis induced by amyloid beta protein in the human neural tumor cell line PAJU. In this study, we examined the role of the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway in this process. Western blot analysis demonstrated that telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidy-linositol-3-kinase/protein kinase B were not expressed in PAJU cells transfected with empty plasmid,while they were expressed in PAJU cells transfected with a telencephalin expression plasmid. After treatment with 1.0 nM amyloid beta protein 42, expression of telencephalin and phosphorylated phosphatidylinositol-3-kinase/protein kinase B in the transfected cells gradually diminished, while levels of phosphorylated ezrin/radixin/moesin increased. In addition, the high levels of telencephalin,phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B expression in PAJU cells transfected with a telencephalin expression plasmid could be suppressed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings indicate that telencephalin activates the ezrin/radixin/moesin family/phosphatidylinositol-3-kinase/protein kinase B pathway and protects PAJU cells from amyloid beta protein-induced apoptosis. Telencephalin is a neural glycoprotein that reduces apoptosis induced by amyloid beta protein in the human neural tumor cell line PAJU. In this study, we examined the role of the ezrin / radixin / moesin protein family / phosphatidylinositol-3-kinase / protein kinase B pathway in this process. Western blot analysis demonstrated that telencephalin, phosphorylated ezrin / radixin / moesin and phosphatidy-linositol-3-kinase / protein kinase B were not expressed in PAJU cells transfected with empty plasmid, while they were expressed in PAJU cells transfected with a After treatment with 1.0 nM amyloid beta protein 42, expression of telephase and phosphorylated phosphatidylinositol-3-kinase / protein kinase B in the transfected cells gradually diminished, while levels of phosphorylated ezrin / radixin / moesin increased. In addition, the high levels of telencephalin, phosphorylated ezrin / radixin / moesin and phosphatidylinositol-3-kinase / protein kinase B expression in PAJU cells s transfected with a telencephalin expression plasmid could be suppressed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings indicate that telencephalin activates the ezrin / radixin / moesin family / phosphatidylinositol-3-kinase / protein kinase B pathway and protects PAJU cells from amyloid beta protein-induced apoptosis.