Cross-linking mass spectrometry analysis has revealed a novel fibrin cross-linking mechanism in trauma patients, driven by TG2 and characterized by unique β-α cross-links. Future efforts should focus on developing TG2/β-α cross-links as innovative biomarkers for TIC, alongside advancing therapeutic strategies targeting TG2. Figure created with biorender.com. Yao, Z. (2025) https://biorender.com/ieilul5.