Mutations in genes implicated in ALS encode proteins with diverse cellular functions with some convergence, however, on RBPs including: TAR DNA-binding protein (TARDBP), fused in sarcoma (FUS), TATA-Box Binding Protein Associated Factor 15 (TAF15), EWS RNA Binding Protein 1 (EWSR1), heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), matrin 3 (MATR3), T-cell-restricted intracellular antigen-1 (TIA1) and senataxin (SETX) (Table 1). The gene discussed is SETX; the disease is amyotrophic lateral sclerosis.