Recent studies have shown that decreased levels of a single cytoplasmic tRNA isoacceptor or deletion/mutation of a single nuclear-encoded tRNA gene is sufficient to alter translation and cause neuronal dysfunction: Dominant mutations in the glycyl-tRNA synthetase gene associated with Charcot-Marie-Tooth disease CMT2D, cause sequestration of tRNAGly, neuropathy, impair neuronal translation and induce the ISR (Spaulding et al., 2021; Zuko et al., 2021). The gene discussed is GARS1; the disease is Charcot-Marie-Tooth disease.