Reduced levels in spinal cords of patients with ALS; irregular and disrupted nuclear staining in sporadic ALS with TDP-43; depletion of KPNB1 directly contributes to impaired nuclear import and cytoplasmic accumulation of TDP-43; ALS-related mutations in FUS reduce its sensitivity to the chaperone activity of KPNB1, ultimately leading to increased phase separation. Here, FUS is linked to amyotrophic lateral sclerosis.