Human Glycosyl Hydrolase family 18 chitinase (GH18 chitinase)

Human Glycosyl Hydrolase family 18 (GH18) chitinases are a group of proteins that include enzymatically active chitinases, such as chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as non-enzymatic chitinase-like proteins (CLPs) like chitinase-3-like protein 1 (CHI3L1/YKL-40) [2, 5]. Although humans do not synthesize chitin, these proteins are expressed by various cells, including macrophages and epithelial cells, and play critical roles in the innate immune response by recognizing and degrading chitin from pathogens like fungi and parasites [4, 11]. Beyond their hydrolytic activity, GH18 members function as signaling molecules and lectins that regulate tissue remodeling, cell proliferation, and Th2-mediated inflammation [2, 16]. Dysregulation of these proteins is linked to several chronic inflammatory and fibrotic diseases, including asthma, idiopathic pulmonary fibrosis, and Gaucher disease, as well as various cancers where they promote tumor progression and metastasis [2, 6, 16]. In therapeutic development, small-molecule inhibitors like OATD-01 are being explored to modulate these pathways, particularly in fibrotic lung diseases [2, 9]. Additionally, these proteins serve as valuable clinical biomarkers, with chitotriosidase activity used to monitor Gaucher disease and YKL-40 levels indicating disease severity in inflammatory and oncological conditions [6, 14].

Other names

ChitotriosidaseAcidic mammalian chitinaseChitinase-3-like protein 1YKL-40CHIT1AMCaseCHIACHI3L1HC-gp39YKL-39CHI3L2Oviduct-specific glycoproteinOVGP1

Competitive inhibition of the catalytic domain in active chitinases (CHIT1 and AMCase) to prevent chitin hydrolysis and downstream inflammatory signaling; blockade of chitin-binding or receptor-interacting sites in chitinase-like proteins (e.g., CHI3L1) to inhibit non-enzymatic signaling pathways involved in tissue remodeling and cell proliferation [2, 4, 9, 16].