TIA1 mutations are rare in human ALS, and mutations are heterozygous, while this study uses a homozygous TIA1 mutant mouse model to amplify pathogenic effects for experimental tractability.<h4>Methods</h4>To explore the mechanisms by which mutant TIA1 causes ALS neurodegeneration, we generated a TIA1 mutant mouse by introducing ALS-causing mutations into the endogenous animal via cytosine base editors. Here, TIA1 is linked to amyotrophic lateral sclerosis.