The ability of AHR agonists to increase insoluble TDP-43 raises the possibility that they could potentiate the pathophysiology of ALS since the accumulation of insoluble TDP-43 is the predominant aggregating species in ALS, and mutations in TDP-43 that increase accumulation of insoluble TDP-43 are sufficient to cause disease in humans. This evidence concerns the gene AHR and amyotrophic lateral sclerosis.