The TDP-43K408R model will therefore help facilitate the exploration of how the exposome synergizes with TDP-43 to better understand how ALS/FTD relevant stressors that humans may experience throughout aging (e.g. C9ORF72 expansions, viral infections, and traumatic brain injury) converge on TDP-43 and uniquely drive aspects of neurodegeneration. Here, TARDBP is linked to amyotrophic lateral sclerosis.