LARS1 (leucyl-tRNA synthetase 1) is an aminoacyl-tRNA synthetase that catalyzes the ATP-dependent attachment of leucine to its cognate tRNA(Leu) through a two-step reaction involving leucyl-adenylate intermediate formation 1. Beyond its canonical protein synthesis role, LARS1 functions as a crucial nutrient sensor integrating leucine and glucose availability to regulate mTORC1 signaling. Under glucose starvation, LARS1 undergoes O-GlcNAcylation at S1042, which promotes ULK1-mediated phosphorylation at leucine-binding sites, reducing leucine affinity and mTORC1 activity while redirecting leucine toward catabolic energy production 23. LARS1 also regulates autophagy and lipophagy through mTORC1 activation 45. Disease associations include infantile liver failure syndrome 1, characterized by developmental delay, seizures, and encephalopathic episodes with characteristic MRI patterns showing deep gray matter and brainstem changes 67. LARS1 dysfunction contributes to cancer progression through multiple mechanisms, including chemoresistance via impaired N-glycosylation 8 and oncogenic signaling in ovarian cancer 9. Additionally, LARS1 lactylation promotes podocyte injury in diabetic kidney disease by inhibiting autophagy 4, while LARS1 deficiency ameliorates chr5 kidney disease by reducing lipid accumulation and fibrosis 5.