We exome sequenced 699 index cases from a cohort of fALS from eleven countries, negative for mutations in all known ALS genes (including SOD1, TDP43, C9ORF72, FUS, PFN1, UBQLN2, OPTN, VCP, and ANG) and the intronic C9ORF72 repeat expansion. Here, UBQLN2 is linked to amyotrophic lateral sclerosis.