FUScinating insights into motor neuron degeneration.

Point mutations in FUS cause amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease—but do they do that by a loss of the protein's normal function, or by endowing it with novel toxic functions, or both? In this issue of The EMBO Journal, Scekic‐Zahirovic et al (2016) report that mutant FUS, but not the complete loss of FUS, triggers motor neuron degeneration in mice, arguing for a toxic gain‐of‐function mechanism.