Genetic mutations linked with TDP-43 proteinopathies and ALS/FTD, including mutations to TARDBP, C9orf72, ataxin 2 (ATXN2) and superoxide dismutase 1 (SOD1), may confer vulnerability to caspase-cleavage of TDP-43. Here, ATXN2 is linked to amyotrophic lateral sclerosis.