To an earlier report that FUS depletion from iPSC-derived motor neurons produces a different RNA signature than a disease-linked FUS mutation (Kapeli et al., 2016), our analyses have identified that the overwhelming majority of gene expression alterations associated with age-dependent motor and cognitive deficits in humanized mutant FUS mice do not overlap with those altered upon depletion of FUS (Kapeli et al., 2016, Lagier-Tourenne et al., 2012). The gene discussed is FUS; the disease is cognition.