SARS2 (seryl-tRNA synthetase 2, mitochondrial) is a mitochondrial aminoacyl-tRNA synthetase that catalyzes the attachment of serine to tRNA(Ser), fulfilling a critical role in mitochondrial protein synthesis. Beyond its primary function, SARS2 exhibits dual substrate specificity, likely aminoacylating tRNA(Sec) with serine to generate misacylated tRNA L-seryl-tRNA(Sec), which undergoes further conversion to selenocysteinyl-tRNA(Sec) for selenoprotein synthesis. The enzyme operates in the mitochondrial matrix through ATP-dependent mechanisms, utilizing its RNA binding and tRNA binding capacities. Functionally, SARS2 catalyzes both canonical seryl-tRNA aminoacylation and mitochondrial seryl-tRNA aminoacylation pathways. Pathologically, mutations in SARS2 are associated with hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome (HUPRA syndrome), indicating that impaired mitochondrial serine incorporation compromises metabolic homeostasis. The clinical significance lies in understanding how defective aminoacylation affects mitochondrial translation fidelity and energy metabolism, potentially explaining the multisystem phenotype observed in HUPRA syndrome patients. Clarifying SARS2's role in selenoprotein biogenesis may further illuminate its involvement in antioxidant defense and thyroid hormone metabolism.