HSP22 (heat shock protein 22), belonging to the superfamily of small heat shock proteins, which has a molecular mass of 21.6 KD and is able to exist in the form of monomer, has multiple functions including molecular chaperones, apoptosis and anti-apoptosis, lifespan extension, antioxidation and so on. In recent years, studies show that HSP22 plays a crucial role in many neurological diseases, such as hereditary nerve endings disease, Alzheimer disease and Charco-Marie-Tooth. This review explores the progress in HSP22 and its involvement in human neurological disease.