Loss-of-function mutations in TBK1 have been identified in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Van Mossevelde et al. compare TBK1-mutation carriers with FTD, ALS or FTD-ALS to patients carrying GRN or C9orf72 mutations. Differences are seen in age of onset, extrapyramidal symptoms, and in memory, language and behaviour.