IRE1, or inositol-requiring enzyme 1, is a type I transmembrane protein kinase and endoribonuclease that plays a crucial role in the unfolded protein response (UPR). When the endoplasmic reticulum (ER) experiences stress due to the accumulation of unfolded or misfolded proteins, IRE1 becomes activated. This activation is a critical cellular mechanism for restoring ER homeostasis and is implicated in various human diseases, including cancer and neurodegenerative disorders. The activation of IRE1 involves its oligomerization and autophosphorylation, which allows it to perform its kinase and RNase activities. IRE1 has been shown to induce both pro-survival and pro-apoptotic cellular responses, which are closely related to numerous human pathologies. In the context of cancer, IRE1 activity has been confirmed to be increased and is associated with tumorigenesis and resistance to chemotherapy. In terms of neurological implications, IRE1 has been linked to neurodegenerative diseases. It is involved in the regulation of central carbon metabolism and diet-induced obesity in mice through its role in chromatin structure and gene expression. Furthermore, IRE1α has been shown to dynamically coalesce with stress granules, which are associated with the cellular response to various stresses, including those relevant to neurodegenerative conditions. In the context of cancer, IRE1 has a dual role in tumor development. It can act as a tumor suppressor by promoting the clearance of cells with high levels of ER stress, and it can also promote tumor growth under certain conditions. The specific outcomes depend on the cellular context and the activation state of IRE1.
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