LARS1, leucyl-tRNA synthetase 1, is an enzyme crucial for protein synthesis, specifically ligating leucine to its cognate tRNA. It also functions as a leucine sensor upstream of the amino acid-sensing pathway, participating in coordinating protein synthesis and autophagy for cell growth [3,7]. LARS1 is involved in multiple pathways, such as mTORC1 regulation in response to glucose and leucine availability [3,4].

In hepatocellular carcinoma (HCC), LARS1 expression is elevated in tumor tissues compared to normal tissues, correlated with various clinicopathological features, and higher expression is linked to worse survival. It may promote HCC through processes like neutral lipid metabolic process and cholesterol metabolism [1].

In ovarian cancer, LARS1 is increased and acts as an oncogene, while the mitochondrial-derived peptide MOTS-c can suppress ovarian cancer progression by promoting LARS1 ubiquitination and degradation [2].

In non-small cell lung cancer, inhibiting LARS1 with BC-LI-0186 in combination with a MEK1/2 inhibitor enhances the anti-tumor effect [5].

Additionally, biallelic variants in LARS1 cause infantile liver failure syndrome type 1 (ILFS1). In a zebrafish model with a LARS1 variant, enhanced autophagy led to hepatic steatosis, suggesting a mechanism for ILFS1-associated hepatic dysfunction [6].

In conclusion, LARS1 is essential for protein synthesis and nutrient-sensing-related cellular processes. Its dysregulation is associated with various cancers and ILFS1. Studies using models like zebrafish with LARS1 variants help reveal its role in disease-related biological processes, providing insights into potential therapeutic strategies for these diseases.