While a defect of mitochondrial protein synthesis in recessive GARS-related mitochondrial disease is most likely a result of loss of function, in dominant neuropathy-causing mutations we identified a defect of the MAM complex, suggesting that mitochondria ER interactions and calcium metabolism, possible due to non-cognate function of GARS may potentially explain tissue-specific clinical manifestations in human motor neurons. Here, GARS1 is linked to inborn mitochondrial metabolism disorder.