The article reviews the unfolded protein response (UPR), a cellular mechanism that helps eukaryotic cells cope with stress caused by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The UPR is triggered when the ER's protein-folding capacity is disrupted, leading to the activation of three main signaling pathways: PERK, IRE1, and ATF6. These pathways work together to restore ER homeostasis by reducing protein synthesis, increasing the production of chaperone proteins, and enhancing the ER's capacity to fold and process proteins. The UPR also plays a critical role in various physiological processes, including the development and function of professional secretory cells such as plasma cells, pancreatic β cells, hepatocytes, and osteoblasts. These cells require a highly evolved mechanism to properly fold, process, and secrete large quantities of proteins, and the UPR is essential for maintaining their function and survival. The article discusses the mechanisms of UPR activation, signal transduction, and termination, as well as the physiological and pathological roles of the UPR in different tissues. It also highlights the importance of the UPR in the development of B cells into plasma cells, the regulation of β cell function and survival in the context of diabetes, and the role of the UPR in hepatocytes and osteoblasts. The study emphasizes the complexity of the UPR and its diverse functions in maintaining cellular homeostasis and responding to various stress conditions.The article reviews the unfolded protein response (UPR), a cellular mechanism that helps eukaryotic cells cope with stress caused by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The UPR is triggered when the ER's protein-folding capacity is disrupted, leading to the activation of three main signaling pathways: PERK, IRE1, and ATF6. These pathways work together to restore ER homeostasis by reducing protein synthesis, increasing the production of chaperone proteins, and enhancing the ER's capacity to fold and process proteins. The UPR also plays a critical role in various physiological processes, including the development and function of professional secretory cells such as plasma cells, pancreatic β cells, hepatocytes, and osteoblasts. These cells require a highly evolved mechanism to properly fold, process, and secrete large quantities of proteins, and the UPR is essential for maintaining their function and survival. The article discusses the mechanisms of UPR activation, signal transduction, and termination, as well as the physiological and pathological roles of the UPR in different tissues. It also highlights the importance of the UPR in the development of B cells into plasma cells, the regulation of β cell function and survival in the context of diabetes, and the role of the UPR in hepatocytes and osteoblasts. The study emphasizes the complexity of the UPR and its diverse functions in maintaining cellular homeostasis and responding to various stress conditions.