Chi3l1, also known as chitinase-3-like protein 1 or YKL-40, belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid. Chi3l1 is synthesized and secreted by various cells and plays major roles in tissue injury, inflammation, repair, and remodeling. It is involved in multiple biological processes and is associated with numerous diseases [4].

In triple-negative breast cancer (TNBC), Chi3l1 ablation in the PyMT breast cancer model generated an anti-tumor immune response, delayed tumor onset, increased T-cell infiltration, and improved response to immune-checkpoint blockade. Mechanistically, Chi3l1 promoted neutrophil recruitment and neutrophil extracellular trap formation, which blocked T-cell infiltration [1].

In the context of Alzheimer's disease, Chi3l1 deletion in mice decreased amyloid plaque burden in the APP/PS1 model, suggesting that Chi3l1 may suppress glial phagocytic activation and promote amyloid accumulation. Also, Chi3l1 expression is regulated by the circadian clock [2].

In multiple sclerosis, astrocytic deletion of Chi3l1 mitigated neurogenic deficits and cognitive dysfunction. CHI3L1 interacts with CRTH2/RAGE, attenuating β-catenin signaling [3].

In conclusion, Chi3l1 is involved in diverse biological processes. Gene-knockout mouse models have revealed its roles in cancer, neurodegenerative diseases like Alzheimer's, and multiple sclerosis. These studies help us understand the disease mechanisms and may provide potential therapeutic targets for these diseases.