We provide evidence for the ability of GM1‐oligosaccharide (GM1‐OS) to prevent the neurodegeneration of an in vitro model of amyotrophic lateral sclerosis (ALS) by acting on crucial processes of disease pathophysiology (excitotoxicity, SOD1 aggregation, TDP43 mislocalization, mitochondria dysfunction, and oxidative stress). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.