Alexander disease (ALXDRD) is a primary astrocytic disease caused by mutations in the glial fibrillary acidic protein (GFAP) gene. Although numerous GFAP mutations have been reported, most are missense mutations, while frameshift mutations, in-frame insertions/deletions and splice site mutations are rare [1]. Additionally, the clinical phenotypes of cases with GFAP mutations exhibit wide variability in age at onset and core neurological features, including spastic paraparesis, cerebellar ataxia, and more rarely, features mimicking progressive supranuclear palsy (PSP) [2]. This report presents a case with a novel in-frame deletion/insertion mutation in the GFAP showing clinical characteristics suggestive of PSP.