In this study, we describe the generation and neural differentiation of diseased SCA-iPSCs with mutations in ATXN2 or ATXN3. Using SCA-iPSCs as an in vitro disease modelling platform, our studies revealed that the SCA-iPSC-derived neuronal populations exhibit vulnerability to glutamate. Here, ATXN2 is linked to autosomal dominant cerebellar ataxia.