Xbp1, also known as X-box binding protein-1, is a transcription factor and a key regulator in the unfolded protein response (UPR) pathway. The UPR is activated upon endoplasmic reticulum (ER) stress to restore ER homeostasis. Xbp1 communicates with conserved signalling components of the UPR and is essential for cell fate determination in response to ER stress [4]. Genetic models, such as knockout (KO) mouse models, are valuable for studying Xbp1's functions.

In non-alcoholic steatohepatitis (NASH), Xbp1 expression is upregulated in human liver tissues. Hepatocyte-specific Xbp1 knockout (Xbp1ΔHep) and macrophage-specific Xbp1 knockout (Xbp1ΔMf) mice show inhibited development of steatohepatitis and fibrosis compared to wild-type mice. Xbp1-deleted macrophages reduce steatohepatitis by decreasing NLRP3 expression, pro-inflammatory cytokine secretion, and preventing hepatic stellate cell activation [1]. In colorectal cancer, Xbp1 activation in tumor-associated macrophages (TAMs) promotes tumor growth and metastasis, while Xbp1 ablation inhibits TAMs' pro-tumor cytokine signature and enhances phagocytosis [2]. In MYC-driven breast cancer, Xbp1 is a synthetic lethal partner of MYC, and silencing Xbp1 selectively blocks the growth of MYC-hyperactivated cells [3].

In conclusion, Xbp1 is crucial in the UPR pathway, affecting cell fate under ER stress. Through gene knockout mouse models, it has been revealed that Xbp1 plays significant roles in diseases like NASH, colorectal cancer, and MYC-driven breast cancer. These studies help understand the mechanisms of these diseases and provide potential therapeutic targets related to Xbp1.