The review discusses the mechanisms by which endoplasmic reticulum (ER) stress-induced apoptosis contributes to various diseases, including neurodegenerative disorders, diabetes, atherosclerosis, and renal disease. It highlights the three branches of the unfolded protein response (UPR): IRE1, PERK, and ATF6. The activation of these pathways can lead to apoptosis through various mechanisms, such as the degradation of mRNA, suppression of the survival protein Bcl-2, and induction of oxidative stress. The review also explores the integration of these pathways and their potential therapeutic implications, emphasizing the need for more comprehensive in vitro and in vivo models to fully understand the complex mechanisms involved in ER-stress-induced apoptosis.The review discusses the mechanisms by which endoplasmic reticulum (ER) stress-induced apoptosis contributes to various diseases, including neurodegenerative disorders, diabetes, atherosclerosis, and renal disease. It highlights the three branches of the unfolded protein response (UPR): IRE1, PERK, and ATF6. The activation of these pathways can lead to apoptosis through various mechanisms, such as the degradation of mRNA, suppression of the survival protein Bcl-2, and induction of oxidative stress. The review also explores the integration of these pathways and their potential therapeutic implications, emphasizing the need for more comprehensive in vitro and in vivo models to fully understand the complex mechanisms involved in ER-stress-induced apoptosis.