Chitinase-like protein (CLP)

Chitinase-like proteins (CLPs) are a group of evolutionarily conserved glycoproteins belonging to the glycosyl hydrolase 18 (GH18) family (UniProt). While they share structural homology with active chitinases, CLPs lack the essential catalytic residues required to hydrolyze chitin, instead functioning as signaling molecules and lectins (PubMed: 22524424). The most extensively studied member, Chitinase-3-like protein 1 (CHI3L1 or YKL-40), is secreted by macrophages, chondrocytes, and cancer cells in response to cytokines like IL-6 and TNF-alpha (NIH: PMC4141375). CLPs play pivotal roles in regulating the innate immune response, promoting cell proliferation, and facilitating tissue remodeling and angiogenesis (PubMed: 30214036). In clinical contexts, elevated levels of CLPs are strongly associated with chronic inflammatory conditions, such as asthma and rheumatoid arthritis, as well as poor prognosis in various malignancies (PubMed: 29104119). Therapeutic development focuses on neutralizing these proteins using monoclonal antibodies or small molecules to disrupt their interaction with receptors like IL-13Rα2 and TMEM219, which drive pathological fibro-inflammatory and oncogenic pathways (PubMed: 32814544).

Other names

Chitinase-3-like protein 1CHI3L1YKL-40Chitinase-3-like protein 2CHI3L2YKL-39Breast regression protein 39Brp-39Stabilin-1-interacting chitinase-like proteinSI-CLP

Neutralization of secreted protein to prevent binding to receptors such as IL-13Rα2, TMEM219, or CD44, thereby inhibiting downstream pro-inflammatory and pro-survival signaling pathways.