Leucyl-tRNA synthetase 1 (LARS1)

Leucyl-tRNA synthetase 1 (LARS1) is a cytosolic enzyme of the class I aminoacyl-tRNA synthetase family that catalyzes the attachment of the amino acid leucine to its cognate tRNA in an ATP-dependent two-step reaction, serving as a critical component of the foundational process of protein translation. LARS1 is also found within the multisynthetase complex and acts as an intracellular leucine sensor, linking amino acid availability to cell signaling through the mTORC1 pathway, thus regulating cellular growth, autophagy, and metabolic homeostasis. Pathogenic variants in LARS1 cause clinical disease including infantile liver failure syndrome; increased expression is observed in cancers such as lung cancer, playing roles in cell growth and migration. No approved direct LARS1 inhibitors are in clinical use, but inhibitors of downstream pathways (such as mTORC1 and autophagy) are being explored in disease models.

Other names

Leucine--tRNA ligase, cytoplasmicLeucyl-tRNA synthetaseLARSLeuRScLRSHSPC192KIAA1352FLJ10595FLJ21788LEUSRNTLSILFS1LEURSLFISLRSPIG44hr025Clproliferation-inducing gene 44cytosolic leucyl-tRNA synthetaseleucine tRNA ligase 1cytoplasmic leucine--tRNA ligase

Inhibition of aminoacylation activity reduces protein synthesis. Modulation of mTORC1 pathway activity via leucine sensing alters anabolic signaling and autophagy. Inhibition of downstream targets (e.g., DGAT1, autophagy inhibitors) ameliorates disease phenotypes in model systems.