{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nX‐box binding protein 1 (XBP1) is a central transcriptional regulator of the unfolded protein response (UPR) that is activated when misfolded proteins accumulate in the endoplasmic reticulum. Under such stress, the ER‐resident sensor IRE1 catalyzes the unconventional splicing of XBP1 messenger RNA to produce its active isoform (XBP1s), which then up‐regulates genes encoding ER chaperones, components of the ER‐associated degradation machinery, and lipid biosynthetic enzymes to restore protein homeostasis. In parallel, the unspliced isoform (XBP1u) can act in a negative feedback loop by sequestering XBP1s and promoting its degradation. In addition, regulatory events such as transient translational pausing, post‐translational modifications (for example, acetylation by p300 and deacetylation by SIRT1), and cross talk with other UPR sensors (including ATF6) and metabolic pathways (via mTORC2) further fine‐tune XBP1’s activity and contribute to ER biogenesis and membrane expansion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in ensuring ER proteostasis, aberrant XBP1 signaling is implicated in diverse pathophysiological conditions. In the gastrointestinal tract, insufficient XBP1 activity in secretory epithelial cells can trigger inflammatory bowel disease, while in metabolic tissues its dysregulation contributes to pancreatic β‐cell dysfunction and hepatic steatosis. In the immune system, XBP1 influences dendritic cell activation, plasma cell differentiation, and T cell anti‐tumor responses. Moreover, XBP1 plays a critical role in cancer biology—it supports tumor cell adaptation to hypoxia in aggressive breast cancers, contributes to multiple myeloma pathogenesis and therapeutic resistance, and is linked to antiestrogen resistance. XBP1 also participates in viral life cycles by acting as a molecular switch for lytic reactivation in herpesvirus‐infected B cells, and its imbalance has been associated with disorders ranging from atherosclerosis and pulmonary fibrosis to bipolar disorder. These multifaceted functions of XBP1 underscore its promise as both a prognostic marker and a target for therapeutic intervention across a spectrum of human diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "H Yoshida, T Matsui, A Yamamoto, et al. 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