Determining the precise amount of reduction in polyQ ATXN1 needed to rescue each cell-specific phenotype, determining when this reduction is needed, and determining whether it needs to be mutant allele specific will be critical for the design of novel and effective gene-based therapies in SCA1 and — potentially — for the broader category of neurodegenerative proteinopathy-based diseases. The gene discussed is ATXN1; the disease is spinocerebellar ataxia type 1.