Recent reports strongly suggest that the ER stress may represent an important mechanism of the altered repair process observed in the alveolar epithelium of fibrotic lung [35] . Situations associated with abnormal regulation of the cascade of events leading to the formation of mature protein result in either misfolding or mistargeting of the protein. These events trigger induction of intracellular aggregate formation and ER stress, which can lead to cell death through apoptosis and autophagic pathways [36, 37] . Several stimuli including oxidant-antioxidant imbalance, viral proteins, inflammatory molecules, nutrient deprivation may induce ER stress [38, 39] ( Figure 2 ). Among the cytoprotective mechanisms available are the ER chaperones such as binding immunoglobulin protein (BiP). Interestingly, mutant BiP mice have been reported to die within several hours of birth from respiratory failure due to impaired secretion of pulmonary surfactant by type 2 AEC. In these animals, expression of surfactant protein (SP)-C was reduced and the lamellar bodies were malformed, indicating that BiP Figure 2 Alveolar structure disorder-associated ILD and ER stress. The (Endoplasmic Reticulum) ER and its protein maturation machinery allow the synthesis of mature secretory and membrane proteins with specific folded conformation. In situations of stress induced by genetic mutations or environmental factors, unfolded or misfolded proteins are retained in the ER and induce a defence mechanism called the ER stress response. The induction of ER chaperones is critical to increase the ER folding capacity allowing the production of correctly folded protein.