Chitinase-3-like protein 1 (CHI3L1)

Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted glycoprotein belonging to the glycoside hydrolase family 18, encoded by the CHI3L1 gene in humans[1][2][5][6]. Despite structural similarity to chitinases, CHI3L1 lacks enzymatic activity toward chitin due to active site mutations but retains chitin-binding capacity[1][2][6]. It is produced by multiple cell types—macrophages, neutrophils, chondrocytes, synovial cells, fibroblasts, vascular smooth muscle cells, and even tumor cells. Biologically, CHI3L1 is implicated in processes such as inflammation, tissue repair, extracellular matrix remodeling, fibrosis, cell proliferation, and angiogenesis[2][3][6]. Elevated CHI3L1 levels are associated with a range of diseases, including cancers, cardiovascular and metabolic disease, neurodegeneration (notably Alzheimer's disease), asthma, and other chronic inflammatory conditions. It is investigated as a disease biomarker and a potential therapeutic target, with investigational inhibitors in development but no approved therapies specifically directed at this molecule. CHI3L1 interacts with several cellular receptors (including IL-13Rα2 and CD44) to mediate its biological effects[2][6]. Its pleiotropic role in health and disease underscores the therapeutic promise as well as the complexity and risks involved in targeting this protein.

Other names

YKL-40YKL40breast regression protein 39 (in mice)chitinase 3-like 1

Under investigation; current approaches target CHI3L1 to inhibit inflammation, tissue remodeling, fibrosis, tumor cell proliferation, and angiogenesis[3][6]. Some investigational agents (antibodies, small molecules) attempt to block CHI3L1 interactions with its binding partners, including interleukin-13 receptor alpha 2 (IL-13Rα2), CD44, and others[2][6].