Emerging roles of stress granules in liver diseases: a comprehensive review

Qianyun Zhang¹Yun Liu²Junzhe Tang¹Ming Li^1,3*Qiang Jia^1,3*

• ¹Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
• ²Hospital-Acquired Infection Control Department, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, China
• ³School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

Stress granules (SGs) are transient, membraneless condensates that assemble dynamically within cells in response to diverse stressors. In recent years, SGs have been found to be closely associated with multiple pathological states and have attracted significant attention, particularly concerning their roles in hepatic pathophysiology. Functioning as critical hubs for post-transcriptional regulation, SGs maintain cellular homeostasis through the sequestration, transport, and translational suppression of mRNA, thereby potentially modulating the initiation and progression of various liver diseases. Our review summarizes the assembly mechanisms of SGs and recent research advances concerning their involvement in diseases including hepatocellular carcinoma, viral hepatitis, acute liver injury and fatty liver disease. It particularly focuses on SGs core RNA-binding proteins and associated regulatory networks. Although research into the impact of SGs on liver diseases remains in a nascent phase, with mechanistic details still elusive, SGs emerge as pivotal molecular nexuses connecting cellular stress responses to pathophysiological states, highlighting their therapeutic potential for liver disorders. This review aims to provide a theoretical foundation for a deeper understanding of the roles of SGs in liver pathologies and to promote their further development in both fundamental research and clinical translation.