XBP1 (X-box binding protein 1) is a transcription factor that serves as a critical mediator of the unfolded protein response (UPR) during endoplasmic reticulum stress, but its roles extend far beyond cellular stress responses. In cancer biology, XBP1 demonstrates complex, context-dependent functions. In triple-negative breast cancer, XBP1 acts as an oncogene by forming transcriptional complexes with HIF1α to regulate hypoxia-response genes, promoting tumorigenicity and poor prognosis 1. Similarly, XBP1 drives colorectal cancer progression by promoting protumoral macrophage functions, including increased IL-6 and VEGFA expression while suppressing phagocytosis 2. However, XBP1 can also function as a tumor suppressor in hematopoietic stem cells, where IRE1α-XBP1 signaling represses pro-leukemogenic programs including Wnt-β-catenin pathways, protecting against acute myeloid leukemia development 3. In metabolic disease, XBP1 promotes non-alcoholic steatohepatitis progression through both hepatocyte lipid metabolism regulation and macrophage-mediated inflammation via NLRP3 signaling 4. XBP1 also impairs T cell anti-tumor immunity by limiting glutamine transport and mitochondrial respiration in the tumor microenvironment 5. These diverse functions highlight XBP1's central role in integrating cellular stress responses with cancer progression, immune function, and metabolic homeostasis.