This gene-pathology-phenotype relationship implies that (1) dysfunctions in TDP-43 and FUS are able to trigger disease cascades as mutations in the TARDBP and FUS genes are causal for ALS and FTD; (2) regardless of the causes, the pathogenic process converges on TDP-43 as pathological TDP-43 inclusions are present in the majority of ALS and FTD patients (to a much lesser extent for FUS); and (3) the pathogenic mechanisms for TDP-43 and FUS are likely to be a combination of both loss-of-function and gain-of-function properties. This evidence concerns the gene FUS and frontotemporal dementia.