There is increasing evidence that epithelial-mesenchymal transition (EMT) plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) by serving as a mechanism for generation of fibroblasts/myofibroblasts, key effector cells in IPF. The receptor for advanced glycation end products (RAGE) purportedly plays an important role in maintaining lung homeostasis whilst ezrin/radixin/moesin (ERM) proteins serve as important crosslinkers between the plasma membrane and cytoskeleton. Given this, we investigated the role of RAGE and ERM proteins in cytokine-induced EMT of alveolar epithelial cells (AECs). Alveolar epithelial cells (A549) were stimulated with TGF-b1 (5 ng/ml) and/or cytomix [IL-1b + TNF-a + IFN-g] (10 ng/ml). Changes in expression of EMT markers were measured using immunofluorescence microscopy (IFM) and western blot (WB). RAGE expression and localisation were evaluated using WB and IFM. Total and phosphorylated ERM levels were assessed using WB. Co-localisation of F-actin and ERM proteins was also investigated. When challenged with TGF-b1 and/or Cytomix, AECs underwent EMT with cells exhibiting decreased levels of E-cadherin, enhanced expression of vimentin and a spindle-shaped phenotype. This was coupled with altered expression of RAGE together with a marked redistribution of ERM proteins from the cytoplasm to the cell periphery. F-actin stress fibres formed following induction of EMT were found to co-localise with ERM proteins. Moreover, ERM proteins were found to undergo phosphorylation following treatment. Together, these results suggest that both RAGE and ERM proteins may play an important role in EMT of AECs in vitro following exposure to TGF-b1 and/or Cytomix. STB is funded by an IRSCET postgraduate scholarship