The second mutation results in an M323K change in TDP‐43 and falls within the C‐terminal LCD where almost all known ALS‐causing mutations are clustered—specifically within a 20 amino acid stretch that influences TDP‐43 alpha‐helix structure which is important for liquid phase separation, aggregation and protein self‐interaction (Conicella et al, 2016). Here, TARDBP is linked to amyotrophic lateral sclerosis.