Patients with enthesitis-related arthritis (ERA) exhibit limited spinal function and clinically observable sacroiliitis,1 and they are predisposed to experiencing higher disease activity, reduced rates of disease remission, and poorer long-term outcomes compared with other subtypes of juvenile idiopathic arthritis. Nevertheless, due to the insidious onset and the subtle clinical manifestations during the early stages of the disease, achieving a timely diagnosis remains a significant challenge for children affected by ERA.2,3 Consequently, there is a pressing necessity to develop innovative, noninvasive diagnostic biomarkers with high efficacy for the screening of children with ERA. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) or tRNA-derived fragments (tRFs), which are abundantly present in serum, have been reported to participate in fundamental regulatory processes and exhibit a strong association with various diseases.4 Recent research suggests that tRFs hold potential as diagnostic biomarkers and may be valuable for monitoring disease progression and determining disease prognosis.4,5 However, data on tRFs in rheumatoid arthritis and ERA remain scarce. Therefore, this study aims to investigate the expression profile of tRFs in children with ERA and assess their potential diagnostic value by examining the distribution of these small non-coding RNAs in ERA serum samples. Additionally, preliminary investigations into related biological functions were conducted using bioinformatics approaches.