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. Autophagy plays a crucial role in cell survival after ER stress, as its inhibition increases cell vulnerability to ER stress. The study also demonstrates that autophagy is involved in the degradation of unfolded proteins in the ER, in addition to ER-associated degradation (ERAD). The findings suggest that autophagy is essential for maintaining cellular homeostasis under ER stress and may have therapeutic implications for diseases such as Parkinson's and Huntington's disease.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. Autophagy plays a crucial role in cell survival after ER stress, as its inhibition increases cell vulnerability to ER stress. The study also demonstrates that autophagy is involved in the degradation of unfolded proteins in the ER, in addition to ER-associated degradation (ERAD). The findings suggest that autophagy is essential for maintaining cellular homeostasis under ER stress and may have therapeutic implications for diseases such as Parkinson's and Huntington's disease.