Following the discovery of TAR DNA binding protein 43 (TDP-43) as the pathogenic link between ALS and frontotemporal dementia (FTD)6, pathological staging of ALS has been described based on the propagation of TDP-43 pathology, and shows that motor cortex involvement is evident in early stages of the disease7. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.