Humanised mouse models can be used to model individual patient mutations, including rare mutations, such as the SOD1-L126delTT mutation found in a single Japanese family with distinctive ALS pathology among SOD1 mutation carriers (Watanabe et al. 2005), and the aggressive FUS-Delta14 mutation from a single sporadic early-onset ALS patient modelled in mice through a partial humanisation knock-in strategy (Devoy et al. 2017). Here, FUS is linked to amyotrophic lateral sclerosis.