Repulsive guidance molecule A (RGMa) regulates actin dynamics via neogenin 1 signalling. A new study found that the cerebrospinal fluid of people with amyotrophic lateral sclerosis (ALS) contained elevated levels of RGMa, which correlated with measures of respiratory dysfunction. In rat primary neurons, recombinant RGMa increased deposition of the ALS-associated mutant superoxide dismutase 1 protein, and this was prevented by supplementation with an actin-stabilizing agent. A neutralizing antibody against RGMa improved the motor function and lifespan of an ALS mouse model, demonstrating its therapeutic potential.