This review provides a comprehensive overview of the role of CHI3L1 in brain diseases, emphasizing its potential as a prognostic biomarker and a promising therapeutic target for various brain diseases, such as tumors, stroke, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, multiple sclerosis, neuromyelitis optica, and HIV-associated dementia. This evidence concerns the gene CHI3L1 and multiple sclerosis.