Chitinase-3-like protein 1 (CHI3L1) (CHI3L1)

Chitinase-3-like protein 1 (CHI3L1), commonly known as YKL-40, is a highly conserved secreted glycoprotein and a member of the glycosyl hydrolase 18 family [1, 10]. Although it lacks the enzymatic chitinase activity of its structural homologs, it functions as a potent biological mediator that regulates inflammation, cell survival, and tissue remodeling by binding to various receptors such as IL-13RA2 and TMEM219 [2, 11]. In oncology, YKL-40 is frequently overexpressed in the tumor microenvironment, where it promotes angiogenesis, metastasis, and the transition of macrophages to a pro-tumorigenic M2 phenotype [1, 6, 11]. Clinically, elevated serum or cerebrospinal fluid levels of YKL-40 serve as significant independent prognostic biomarkers for cancer severity and neurodegenerative progression in diseases like Alzheimer's [4, 10, 18]. Therapeutic strategies currently under development include neutralizing monoclonal antibodies and small molecule inhibitors aimed at blocking the protein's interaction with its receptors to suppress pathological signaling [7, 12, 15].

Other names

YKL-40Cartilage glycoprotein-39CGP-39Chitinase-3-like 1ChondrexGP-3938-kDa heparin-binding glycoproteinHuman cartilage glycoprotein-39HC gp-39Breast regression protein 39

Inhibition of CHI3L1 binding to its receptors (IL-13RA2, TMEM219, Galectin-3, or CD44) to disrupt downstream STAT3, MAPK/ERK, and NF-κB signaling pathways [1, 2, 7, 11].