Insight into ALS changed dramatically in 2006 when the 43 kDa TAR-DNA-binding protein(TDP-43) was identified as a protein that accumulates abnormally in theubiquitinated pathological lesions that characterize brain and spinal cord tissue ofalmost every non-SOD1 ALS patient [3]–[5]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.