biostudies-literatureGao LNational Natural Science Foundation of China1323https://www.ebi.ac.uk/biostudies/studies/S-EPMC12467997biostudies-literatureUnknown15(9)Aminoacyl-tRNA synthetases (AARSs), traditionally recognized for their essential role in protein synthesis, are now emerging as critical players in cancer pathogenesis through translation-independent functions. Lactate-derived lactylation, a post-translational modification, plays an increasingly important role in tumorigenesis in the context of high levels of lactate in tumor cells due to the Warburg effect. Current research has highlighted AARS1/2 as lactate sensors and lactyltransferases that catalyze global lysine lactylation in cancer cells and promote cancer proliferation, providing a new perspective for cancer therapy. This review synthesizes the canonical and non-canonical functions of AARS1/2, with a particular focus on their lactylation-related mechanisms; details how lactylation BiomoleculesAARS1 and AARS2: From Protein Synthesis to Lactylation-Driven Oncogenesis.PMC1246799782170966Guo JGao LJia RfalseAARS1 and AARS2: From Protein Synthesis to Lactylation-Driven Oncogenesis.Aminoacyl-tRNA synthetases (AARSs), traditionally recognized for their essential role in protein synthesis, are now emerging as critical players in cancer pathogenesis through translation-independent functions. Lactate-derived lactylation, a post-translational modification, plays an increasingly important role in tumorigenesis in the context of high levels of lactate in tumor cells due to the Warburg effect. Current research has highlighted AARS1/2 as lactate sensors and lactyltransferases that catalyze global lysine lactylation in cancer cells and promote cancer proliferation, providing a new perspective for cancer therapy. This review synthesizes the canonical and non-canonical functions of AARS1/2, with a particular focus on their lactylation-related mechanisms; details how lactylation 2025-01-01T00:00:00Z2025 Sep2026-05-02T03:09:32.207Z2026-05-02T03:07:36.926ZS-EPMC124679974100863010.3390/biom15091323