We identified 2 novel TARDBP missense mutations (p.N345K and p.I383V) and the known p.M337V mutation in 3 out of 92 familial ALS patients (3.3%), while no mutations were identified in 24 sporadic ALS patients or 180 patients with other neurodegenerative diseases. Here, TARDBP is linked to amyotrophic lateral sclerosis.