QRSL1 (glutaminyl-tRNA amidotransferase subunit QRSL1) is a mitochondrial protein that catalyzes the transamidation of misacylated glutamyl-tRNA(Gln) to correctly charged glutaminyl-tRNA(Gln), a critical step in mitochondrial protein synthesis 1. This reaction occurs through an activated gamma-phospho-glutamyl-tRNA(Gln) intermediate in the presence of glutamine and ATP [UniProt annotation]. QRSL1 functions as a subunit of the GatCAB aminoacyl-tRNA amidotransferase complex, which is essential for charging the single mitochondrial tRNA species that accepts glutamine 1. Biallelic QRSL1 mutations cause combined oxidative phosphorylation deficiency 40 (COXPD40), a severe mitochondrial disorder 2. Patients with QRSL1 defects present with early-onset cardiomyopathy, lactic acidosis, developmental delay, hearing loss, and biochemically confirmed respiratory chain enzyme deficiencies 32. Functional studies demonstrate impaired aminoacylation of mt-tRNAGln and deficient mitochondrial protein translation, which can be partially restored with high glutamine supplementation 1. While historically considered invariably lethal in infancy, recent cases suggest variable outcomes, with some patients surviving into childhood with supportive care 2. The heart and brain appear particularly vulnerable to QRSL1 deficiency due to high mitochondrial biogenesis demands during development 3. Early genetic diagnosis is crucial for tailoring mitochondrial disease management and potential therapeutic interventions.