Chitinases and chitinase-like proteins (C/CLPs)

Chitinases and chitinase-like proteins (C/CLPs) are a group of evolutionarily conserved proteins belonging to the glycosyl hydrolase 18 (GH18) family (Kzhyshkowska et al., 2016, PubMed). In humans, this group includes enzymatically active chitinases, such as chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), which degrade chitin, as well as chitinase-like proteins (CLPs) like YKL-40 (CHI3L1) that lack enzymatic activity but function as potent signaling molecules (UniProt P36222; UniProt Q9BPU0). These proteins are primarily secreted by macrophages, neutrophils, and epithelial cells in response to inflammatory stimuli and are involved in regulating the innate and adaptive immune systems, tissue remodeling, and cell survival (Elias et al., 2005, PubMed). C/CLPs are significantly upregulated in various pathological conditions, including chronic inflammatory diseases like asthma and sarcoidosis, fibrotic disorders such as idiopathic pulmonary fibrosis, and several types of cancer where they promote tumor progression and metastasis (Zhao et al., 2020, PubMed; Mazur et al., 2021, PubMed). Consequently, they have emerged as both valuable biomarkers for disease severity and promising therapeutic targets. Current pharmacological strategies include the development of small molecule inhibitors like OATD-01 to block the enzymatic activity of CHIT1 and AMCase, as well as research into monoclonal antibodies designed to neutralize the pro-inflammatory and pro-fibrotic signaling of YKL-40 (Guan et al., 2022, PubMed).

Other names

Glycosyl hydrolase family 18GH18Mammalian chitinasesChitinase-like lectinsChitinase-3-like protein 1 (CHI3L1)Acidic mammalian chitinase (AMCase)Chitotriosidase (CHIT1)YKL-40YKL-39 (CHI3L2)

Small molecule inhibition of enzymatic chitinolytic activity (targeting CHIT1 and AMCase) and neutralization of chitinase-like protein signaling pathways via monoclonal antibodies or competitive binding.