An aggregating proteinopathy involving the TAR DNA-binding protein (TDP-43) provides a molecular link between two progressive neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) of the motor cortex, brainstem and spinal cord, and frontotemporal lobar degeneration (FTLD) of the frontal, insular, and temporal cortex (non-SOD1 ALS and non-tau FTLD, termed ALS-FTLD; [3, 13, 15, 22, 43]). Here, SOD1 is linked to amyotrophic lateral sclerosis.