Transfer RNA-derived small RNA serves as potential non-invasive diagnostic marker and a novel therapeutic target for acute pancreatitis.

Transfer RNA (tRNA)-derived fragments, a new type of tRNA-derived small RNA (tsRNA), can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels. tsRNAs are not only degradation fragments but also have biological functions, including those in immune inflammation, metabolic disorders, and cell death. tsRNA dysregulation is closely associated with multiple diseases, including various cancers and acute pancreatitis (AP). AP is a common gastrointestinal disease, and its incidence increases annually. AP development is associated with tsRNAs, which regulate cell injury and induce inflammation, especially pyroptosis and ferroptosis. Notably, serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP. We show the characteristics of tsRNAs and their diagnostic value and function in AP, and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.