Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disease that arises from a mutation within the ATXN2 gene characterised by abnormally long CAG trinucleotide repeats. The mutant gene product is the ataxin-2 protein, which bears an expanded glutamine tract. The mutant protein is known to disrupt molecular pathways within cells, leading to cellular death and neurodegeneration within specific brain regions.To cope with disrupted pathways, cells have mechanisms such as the Integrated Stress Response (IRS), which help cells resolve stress situations by reorganising translation to promote cellular survival. A key player within ISR is Stress Granules (SGs), which are dynamic transient membraneless organelles that regulate mRNA metabolism. SGs are enriched in dendrites and synapses. Within neurons, mechanisms of mRNA translation are tightly orchestrated and locally regulated, as these cells share long distances between the different cellular compartments; thus, local protein synthesis is required. Importantly, ataxin-2 plays a role in mRNA translation, and it is known to be a SGs component.In this work, we developed genetic tools to induce or inhibit SGs and manipulate their assembly and disassembly in the context of SCA2 disease, thus evaluating their impact on the disease. We found that GADD34 overexpression was able to inhibit SGs formation, whereas EIF2α led to SGs induction. Both strategies were used in cellular and in vivo models of SCA2 to understand the impact of manipulating SGs formation in the context of the disease phenotype, namely in motor performance, neurodegeneration, and synaptic activity.