Autophagy is activated as a novel signaling pathway in response to endoplasmic reticulum (ER) stress. This study shows that ER stress induces autophagy in neuroblastoma cells, as evidenced by the formation of autophagosomes and the conversion of LC3-I to LC3-II. The IRE1-JNK pathway is required for this autophagy activation, while the PERK and ATF6 pathways do not play a significant role. Inhibition of autophagy makes cells more vulnerable to ER stress, indicating its importance in cell survival. Autophagy is a cellular process that degrades cytoplasmic components and is involved in various physiological functions, including development and disease. The study also shows that autophagy is activated in response to ER stress through the IRE1-JNK pathway, and that this activation is necessary for cell survival but not for apoptosis. The findings suggest that autophagy plays a critical role in protecting cells from ER stress-induced death. The study highlights the importance of autophagy in maintaining cellular homeostasis and its potential therapeutic relevance in diseases associated with ER stress.Autophagy is activated as a novel signaling pathway in response to endoplasmic reticulum (ER) stress. This study shows that ER stress induces autophagy in neuroblastoma cells, as evidenced by the formation of autophagosomes and the conversion of LC3-I to LC3-II. The IRE1-JNK pathway is required for this autophagy activation, while the PERK and ATF6 pathways do not play a significant role. Inhibition of autophagy makes cells more vulnerable to ER stress, indicating its importance in cell survival. Autophagy is a cellular process that degrades cytoplasmic components and is involved in various physiological functions, including development and disease. The study also shows that autophagy is activated in response to ER stress through the IRE1-JNK pathway, and that this activation is necessary for cell survival but not for apoptosis. The findings suggest that autophagy plays a critical role in protecting cells from ER stress-induced death. The study highlights the importance of autophagy in maintaining cellular homeostasis and its potential therapeutic relevance in diseases associated with ER stress.