Amyotrophic Lateral Sclerosis (ALS) is a progressively fatal neurodegenerative disease characterized by aggregates of a protein called TDP-43. ALS also features the presence of several inflammatory cytokines in the central nervous system. In this project, we will study how TDP-43 abnormally mislocalizes within cells, releasing mitochondrial DNA and triggering a novel pathway of inflammation. We propose that targeting this pathway could lead to new treatments for ALS.