Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly fatal disease of the motor nervous system. The vast majority of ALS is apparently sporadic, but rare familial cases provide important insights into disease pathogenesis. More than 40 different genes, which span a wide range of molecular mechanisms and sub-cellular localization, cause the clinical disease ALS. However, the different genetic variants of ALS appear quite similar clinically. We believe that treatment targets that are conserved across a range of familial ALS variants may also be important in sporadic ALS. In order to identify molecular treatment targets that might be effective against the majority of ALS cases, we will use motor neurons made from ALS patients harboring three different gene mutations, namely, superoxide dismutase 1 (SOD1), tar-binding protein (TDP-43), and Profilin 1 (PFN1). We will identify shared mechanistic pathways that are common across the three ALS variants. By up-regulating or down-regulating the identified targets, we will confirm that individual targets are capable of mitigating phenotypes in the different ALS variants.