The homology model of human IARS2 allows the observation that the Glu708Lys variant, a variant associated with Leigh syndrome, affects a glutamic acid directly involved in the binding of mt-tRNAIle (at the level of nucleotide G69 as inferred from the crystal structure of the complex of tRNAIle with a bacterial isoleucine tRNA ligase, PDB code 1FFY), and is also very close to the catalytically important KMSKS motif and also nearby the binding site of Ile-AMP (Fig. 3b). Here, IARS2 is linked to Leigh syndrome.