Leucyl-tRNA synthetase 2, mitochondrial (LARS2)

Leucyl-tRNA synthetase 2, mitochondrial (LARS2) is an enzyme belonging to the aminoacyl-tRNA synthetase family that specifically catalyzes the attachment of leucine to its corresponding mitochondrial tRNA (tRNA^Leu), a critical step for translating mitochondrial-encoded proteins and supporting oxidative phosphorylation[8][6][2]. Proper function of LARS2 ensures the integrity of mitochondrial energy production and cellular homeostasis[1][8]. Mutations in the LARS2 gene are linked to Perrault syndrome (sensorineural hearing loss and ovarian failure), various multisystem mitochondrial disorders (e.g., lactic acidosis, sideroblastic anemia), as well as neuropsychiatric and neurodegenerative conditions (notably Alzheimer’s disease), primarily via disruption of mitochondrial protein synthesis and energy generation[5][8][1][3]. Experimental disruption of LARS2 alters neuronal mitochondrial function, increases reactive oxygen species, and affects key survival pathways such as PI3K-AKT, highlighting its relevance as a prospective therapeutic target in neurodegeneration and mitochondrial disease[1][7].

Other names

KIAA0028Leucine--tRNA ligase, mitochondrialLeuRSLEURSMGC26121mtLeuRSleucine tRNA ligase 2, mitochondrialHLASAPRLTS4leucine translaseprobable leucine--tRNA ligase, mitochondrialprobable leucyl-tRNA synthetase, mitochondrial[8]

Not established for clinical drugs; mainly described for experimental modulation such as LARS2 overexpression or knockdown affecting mitochondrial translation, redox status, and PI3K-AKT-GSK3β signaling in cell models[1]