Demonstration that dioxin/PCB family environmental toxicants increase the accumulation of TARDBP transcript and TDP-43 protein provides a mechanism for this epidemiological observation, and supports the hypothesis that compounds in the dioxin/PCB family are able to increase the expression and accumulation of TDP-43, which in turn potentiates the pathophysiology of ALS. Here, TARDBP is linked to amyotrophic lateral sclerosis.