In skin biopsies taken during life from 17 individuals who went on to develop ALS we identify TDP-43 pathology from all 17 individuals in a wide distribution of anatomical sites, up to 26.5 years before ALS diagnosis – a presymptomatic period comparable to that observed for skin α-synucleinopathy in Parkinson’s disease. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.