Since HLDs are not only caused by mutations in genes encoding Pol III subunits, but also by alterations in several aaRS1 genes (e.g. DARS1; EPRS1; RARS1; Taft et al., 2013; Wolf et al., 2014a; Mendes et al., 2018, 2020), it has been speculated that changes in tRNA abundance (POLR3-HLD) or dysfunctions in the attachment of amino acids to tRNAs (HLD caused by aaRS1 mutations) could represent a unified disease-causing mechanism, in which reduced availability of specific aminoacylated tRNA(s) would lead to altered or insufficient translation by stalling ribosomes on the corresponding codons. Here, AARS1 is linked to leukodystrophy.