Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYSTis responsible for Chédiak–Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYSTmutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYSTmutations in HSP, finding six adult patients with LYSTmutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYSTmutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.