In this work, the authors we used patient-derived induced- pluripotent stem cells (iPSCs) and directed differentiation to develop human astrocyte and brain- organoid models of giant- axonal neuropathy (GAN), which is caused by KLHL16 gene mutations. These models reproduce abnormalities of the intermediate- filament cytoskeleton similar to astrocytes of GAN patients in vivo. The studies reveal new mechanisms regarding the role of vimentin in glial fibrillary acidic- protein (GFAP) aggregation and KLHL16mRNA localization in cells.