Although genetic mutations are present throughout life, ALS most commonly develops in mid-adulthood (50–60 years), implying that the normal aging process renders MNs vulnerable to degeneration. However, there is considerable variability in disease progression amongst mutation carriers, even within the same families. Hence, this implies that there is no simple correlation between genetics and disease phenotypes, suggesting that environmental factors and the normal aging process are relevant to understand neuronal vulnerability in ALS/FTD.