In conclusion, in our population-based cohort of patients of Italian ancestry, we found that patients with ALS carrying an intermediate ATXN2 polyQ number of repeats≥31 have a distinctive phenotype, characterised by a more rapid disease course, with a 1.5-fold increase of ΔALSFRS-R rate and a higher ΔKing’s. Here, ATXN2 is linked to amyotrophic lateral sclerosis.