FOSB and amyotrophic lateral sclerosis: • Identification of aberrant axon branching and increased levels of Fos-b mRNA. Overexpression of Fos-b produced aberrant axon branching in vivo and siRNA treatment ameliorated the observed phenotype. • Provide a complete RNA profile of human motor neurons, provides a novel strategy for neurodegenerative axon analysis and present Fos-b pathway as potential therapeutic target in future ALS research.