FUS and neurodegenerative disease: Thus, while we cannot rule out FUS aggregates in the cytoplasm in forms undetectable by our analyses, large aggregates similar to those seen at end-stage disease in patients are not required for disease initiation, consistent with several other neurodegenerative diseases in which large inclusions correlate poorly with either onset or severity of neurodegeneration (Arnold et al., 2013, Arrasate et al., 2004, Kirkitadze et al., 2002, Parone et al., 2013).