Having established the sufficiency of a parsimonious biophysical mechanism by which Kapβ2 regulates self-assembly of wild-type FUS, we next asked whether this control is disrupted for the ALS-linked variant FUSP525L, which carries a mutation within the PY-NLS and causes aggressive, early-onset disease in patients as young as 11 years of age42. Here, FUS is linked to amyotrophic lateral sclerosis.