Protein misfolding and aggregation in cells can be triggered by the oxidative stress caused by free radicals that are produced as a bi-product of metabolism. Free radical removal is therefore essential and is achieved predominantly by the action of the enzyme superoxide dismutase 1 (Sod1). A number of mutations in the human SOD1 gene (hSOD1) have been implicated in the motor neuron disease Amyotrophic Lateral Sclerosis (ALS). The most widely studied hSOD1 mutation in ALS is a G93A substitution. This mutation causes the enzyme to aggregate by an unknown mechanism leading to an increased susceptibility of the cells to oxidative stress. We are developing the yeast Saccharomyces cerevisiae as a model to further investigate the disease-associated alterations in Sod1p structure and function and the impact on the host cell. Expressing the hSOD1G93A mutant in a yeast ∆sod1 mutant background leads to a toxic gain of function and we are currently analysing the underlying mechanism. Developing a yeast/ALS model will allow mutant specific interactions to be studied alongside the cell response to the protein aggregation.