Sarm1 mutations are not common in ALS patients, but a careful examination of the ones that do occur by Dr. Joseph Bloom and colleagues has shown that they tend to cause Sarm1 to be constitutively active and occur more frequently in ALS patients than in the general population. This research, published in Molecular Neurodegeneration, suggests that overactivation of Sarm1 can be a contributing factor to ALS pathology and that blocking Sarm1 activity in ALS may have therapeutic potential.