An increasing body of evidence indicates that TDP-43 proteinopathy underlies motor neuron degeneration caused by diverse genetic defects in various hereditary ALS, including ubiquilin 2 [26], profilin-1 [27], optineurin [28], valosin-containing protein (VCP) [29], and C9ORF72 [30]. This evidence concerns the gene OPTN and amyotrophic lateral sclerosis.