Charcot–Marie–Tooth (CMT) disease is a heterogeneous group of inherited disorders affecting the peripheral nervous system and characterized by distal motor and sensory dysfunction (Charcot and Marie, 1886; Tooth, 1886). Type 2 axonal CMT (CMT2) accounts for 20% of all CMT cases, and it causes progressive muscle weakness and wasting, with sensory deficits in distal limbs resulting from peripheral axon degeneration (Murakami et al., 1996; Fledrich et al., 2012). Because of its phenotypic and genetic heterogeneity, the pathogenesis of CMT remains poorly understood. Despite first being described more than a century ago, there is still no effective treatment for the disease. The study by Spaulding et al.(2016) focused on axonal type 2D CMT (CMT2D), which is caused by dominant mutations in the Glycyl tRNA synthetase (GARS) gene (Antonellis et al., 2003; Griffin et al., 2014). Although several attempts have been made to correlate specific genotypes with phenotypes observed in CMT2D, how a ubiquitously expressed protein necessary for protein translation results selectively in axonal neuropathy remains unclear. To understand the cellular and molecular mechanism linking GARS to CMT2D, Spaulding et al.(2016) used two mouse models with Gars mutations, GarsP278KY and GarsC201R, both of which have motor and sensory deficits of varied severity similar to those observed in patients. Mice carrying theGarsC201R allele (GARSC157R in humans), exhibits the same traits as GarsP278KY mice, but with less severity (Achilli et al., 2009). Spaulding et al.(2016) found that both mutant strains displayed a loss of neuromuscular junction (NMJ) integrity, which was attributed to presynaptic deficits. Although previous research has identified the NMJ as an early and important site in neuropathology, it has not been considered a major site of CMT pathology (Sleigh et al., 2014). Nevertheless, NMJ loss has also been reported in type 1 CMT mouse models (Ang et al., 2010), indicating that this may be a common mechanism of disease. The presence of NMJ abnormalities suggests that more detailed study of the pathological events occurring at these sites will provide a greater understanding of the mechanisms underlying CMT, possibly identifying new therapeutic targets.