YKL-40, also known as chitinase 3-like protein 1 (CHI3L1), is a secreted glycoprotein belonging to the glycoside hydrolase family 18[@chitinase2020]. Despite lacking enzymatic chitinase activity, YKL-40 has emerged as an important biomarker for inflammation, tissue remodeling, and more recently, neurodegenerative diseases[@ykl2021]. It is expressed by various cell types including macrophages, neutrophils, chondrocytes, and certain [neurons](/entities/neurons), where it participates in cellular responses to injury and disease[@chil2019].
Gene and Expression
The human CHI3L1 gene is located on chromosome 1q32.1 and encodes a protein of 383 amino acids. Expression is regulated by:
YKL-40, also known as chitinase 3-like protein 1 (CHI3L1), is a secreted glycoprotein belonging to the glycoside hydrolase family 18[@chitinase2020]. Despite lacking enzymatic chitinase activity, YKL-40 has emerged as an important biomarker for inflammation, tissue remodeling, and more recently, neurodegenerative diseases[@ykl2021]. It is expressed by various cell types including macrophages, neutrophils, chondrocytes, and certain [neurons](/entities/neurons), where it participates in cellular responses to injury and disease[@chil2019].
Gene and Expression
The human CHI3L1 gene is located on chromosome 1q32.1 and encodes a protein of 383 amino acids. Expression is regulated by:
Inflammatory cytokines: IL-6, IL-1β, and TNF-α upregulate expression
Growth factors: TGF-β and PDGF modulate CHI3L1 levels
Cellular stress: Hypoxia and oxidative stress induce expression
Tissue-specific factors: Different cell types show distinct regulation patterns[@chil2020]
Structure
YKL-40 possesses a distinctive structure:
Signal peptide: 20 amino acid N-terminal signal sequence for secretion
Chitinase-like domain: The defining feature with the conserved GH18 fold
Theonine-rich region: O-glycosylated region
Hinge region: Flexible linker between domains
Heparin-binding site: Enables interaction with proteoglycans
The protein lacks the catalytic glutamic acid residue required for chitinase activity, hence it is termed a chitinase-like protein rather than a true enzyme[@ykl2018].
Biological Functions
Inflammation and Immune Response
YKL-40 serves multiple functions in inflammatory processes:
Macrophage activation: Promotes M2 polarization and tissue repair