Aspartyl-tRNA synthetase 2, mitochondrial (DARS2)

Aspartyl-tRNA synthetase 2, mitochondrial (DARS2) is a nuclear-encoded mitochondrial enzyme in the class-II aminoacyl-tRNA synthetase family that catalyzes the attachment of aspartic acid to its specific tRNA, a critical step for the translation of mitochondrial proteins essential for cellular respiration and energy production[1][2][4]. DARS2’s proper function is indispensable for central nervous system white matter integrity, maintenance of hematopoietic stem cells, and regulation of mitochondrial metabolism—including iron-sulfur cluster biogenesis and RNA splicing[1][5][7]. Mutations in DARS2 cause a rare autosomal recessive leukodystrophy (LBSL), manifesting as progressive neurodegeneration due to defective mitochondrial translation[1][4][9]. Altered DARS2 expression is also implicated in cancer biology, affecting cell proliferation and apoptosis[2][6]. In inflammation and infection, DARS2 can be released extracellularly and may serve as a circulating immune modulator[10]. No clinically approved drugs directly target DARS2, but modulation of its degradation may have potential in immunostimulation during severe infections[10].

Other names

Aspartate--tRNA ligase, mitochondrialmtAspRSAspRSFLJ10514aspartyl-tRNA synthetase, mitochondrialLBSLASPRSMT-ASPRS

Not applicable for marketed drugs; experimental immunomodulation by stabilizing DARS2 protein via E3 ligase (FBXO24) inhibition