Amyotrophic lateral sclerosis (ALS) is a lethal, rapidly progressive neuro-degenerative disease with no cure. It is characterised by the selective death of motor neurons in the motor cortex and spinal cord. A large body of literature suggests that ALS pathology is initially linked with neuroinflammation and dysfunction of glia such as astrocytes. However the actual cause of astrocyte dysfunction remains unclear. Mutations in the superoxide dismutase 1 (SOD1) gene account for 20% of familial cases of ALS and misfolded SOD1 has been associated with sporadic ALS. As protein aggregates have recently been shown to be released from neurons we sought to determine the effect of aggregated SOD1 on astrocytes. When added to cultures, aggregated SOD1 was internalized rapidly and remained within primary astrocytes for up to 96 hours. Internalized aggregated SOD1 escaped in to the cytosol and induced a toxic effect. This work may provide a potential link between astrocyte dysfunction and protein aggregation in ALS.