TARDBP and amyotrophic lateral sclerosis type 4: We have shown that transgenic expression of the R2136H mutation and knock-in of the L389S mutation are both sufficient to produce ALS4 disease phenotypes in mice, presenting as slowly progressive motor neuronopathies with the hallmark TDP-43 histopathology seen in sporadic ALS and most forms of familial ALS—TDP-43 nuclear clearing and cytosolic aggregation [3].