CHI3L1 is a non-enzymatic chitinase-like protein that binds chitin, heparin, and hyaluronic acid 1. Despite lacking enzymatic activity, it plays critical roles in tissue remodeling, inflammation, and immune regulation 1. CHI3L1 promotes Th2-mediated inflammatory responses and regulates macrophage polarization; M2 macrophage-derived CHI3L1 improves hepatocellular metabolism and reduces ischemia-reperfusion injury 2. The protein signals through multiple receptors including IL-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, and CD44 1, activating downstream pathways including STAT3 and NF-κB 3. In cancer, CHI3L1 promotes tumor progression through mechanisms including neutrophil recruitment and neutrophil extracellular trap formation that restrict CD8+ T cell infiltration 4, and enhances macrophage activation and angiogenesis 1. CHI3L1 is clinically significant as a biomarker for multiple diseases: elevated expression associates with asthma, arthritis, sepsis, diabetes, and liver fibrosis 1; in neuroinflammation, astrocyte-derived CHI3L1 impairs neurogenesis and cognition in multiple sclerosis by attenuating β-catenin signaling 5, while increased CSF CHI3L1 correlates with Alzheimer's disease progression 6. CHI3L1 emerges as a therapeutic target, with targeted inhibition showing promise in glioblastoma and cancer immunotherapy 14.