Disulfidptosis in hepatocellular carcinoma: molecular mechanisms, therapeutic potential, and exploratory insights into chronic liver diseases.

Disulfidptosis, a newly identified form of programmed cell death (PCD) that was discovered in 2023, occurs specifically in cells with high SLC7A11 expression when glucose is scarce. The underlying mechanism involves NADPH depletion, which triggers severe disulfide stress and ultimately causes the actin cytoskeleton to collapse. In recent years, researchers have increasingly focused on the potential role of disulfidptosis in liver diseases. Current evidence mainly supports its involvement in hepatocellular carcinoma (HCC), with some preliminary data also suggesting connections to liver cirrhosis and metabolic liver disorders. This review critically synthesizes the molecular mechanisms underlying disulfidptosis, explores its possible links to various liver conditions based on the available evidence, and assesses the potential of disulfidptosis-related genes (DRGs) as exploratory tools for diagnosis, prognostic stratification, and exploratory therapeutic prediction. Together, these insights provide a foundation for understanding liver disease pathogenesis and may guide future research efforts, pending rigorous experimental and clinical validation.