Genetic studies across yeast, Drosophila melanogaster and mouse models for CMT2D indicate that, although neuropathy-causing mutations can abolish canonical GlyRS function and loss-of-function pathogenesis hypotheses prevail (Meyer-Schuman and Antonellis, 2017), the disease is most likely caused by a toxic gain-of-function (Boczonadi et al., 2018; Wei et al., 2019). The gene discussed is GARS1; the disease is Charcot-Marie-Tooth disease type 2D.