药物性肝损伤 (DILI) 和病毒性肝脏感染的流行对现代医疗保健提出了重大挑战，并导致全球范围内相当大的发病率和死亡率。与此同时，代谢功能障碍相关的脂肪肝病（MAFLD）已成为一个主要的公共卫生问题，反映了肥胖率的增加并导致更严重的并发症，如纤维化和肝细胞癌。 X-box 结合蛋白 1 (XBP1) 是一种具有碱性区域亮氨酸拉链结构的独特转录因子，其活性通过选择性剪接来调节，以响应内质网 (ER) 稳态的破坏和未折叠蛋白反应 (UPR) 的激活。 XBP1 与高度保守的 UPR 的关键信号传导成分相互作用，在肝脏疾病中响应 ER 应激时，对于决定细胞命运至关重要。本综述旨在阐明 XBP1 在肝脏发病机制中的新作用和分子机制，重点关注其与 DILI、病毒性肝脏感染、MAFLD、纤维化/肝硬化和肝癌的关系。了解 XBP1 在这些肝脏疾病中的多方面功能可以为恢复 ER 稳态和减轻肝损伤的潜在治疗策略提供见解。

The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MAFLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.