Conditional global knockout of TDP-43 in adult mice is lethal after 9 days of TDP-43 inactivation (Chiang et al., 2010) and cell-type specific TDP-43 knockout in motor neurons causes ALS-like motor neuron death (Wu et al., 2012; Iguchi et al., 2013), but the cause of death in these models remains unclear. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.