To understand why some point mutations on the intrinsically disordered TDP-43 prion-domain are sufficient to trigger ALS, we successfully generated recombinant proteins of three ALS-causing mutants, A315E in the Ω-loop, Q331K in the middle of the helix, and M337V in the C-half of the helix (S2A Fig). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.