YARS1 and Charcot-Marie-Tooth disease: As illustrated by the studies on GlyRS-linked CMT and by the network of genes and transcription factors identified in our transcriptome analysis for the mutant TyrRS, aaRS-linked CMT is likely a result of the interplay of multiple molecular pathways—some of them active in the WT condition but dysregulated by the aberrant binding properties of the mutant, while others unique to the mutants alone—and therefore the design of a successful therapeutic approach in the future should be tailored to the pleiotropic mutational impact.