At first, our clinical and in vitro results indicate that the NSCLC mutations P53, KRAS, STK11, EGFR, PI3KCA are not directly involved in the activation of the UPR and the IRE1-sXBP1 axis, while it has been shown that loss of tumor suppressors such as P532 or overexpression of oncogenic HRAS or BRAF3,33 enhance protein translation and synthesis, a key driver of ER stress and tumorigenicity4,34. The gene discussed is ERN1; the disease is neoplasm.