Insights into recent findings and therapeutic opportunities of AARS1 as a lactyltransferase in cancer

Lysine lactylation is a recently discovered post-translational modification with broad implications in cancer biology. Emerging evidence indicates that the canonical alanyl-tRNA synthetase (AARS1) also functions as a lactyltransferase. Notably, lysine lactylation catalyzed by AARS1 has been implicated in cancer progression. Recent findings elucidate the mechanism by which lactate transitions from a metabolic byproduct to a signaling molecule, highlighting AARS1’s central role in metabolic reprogramming, tumor progression, and immune regulation. A deeper understanding of AARS1-mediated lactylation substrates, regulatory networks, and functional variations across tissues and disease states will provide new insights for developing precision interventions targeting lactylation pathways. This review integrates emerging evidence on AARS1 as a lactyltransferase, assessing its clinical implications and proposing therapeutic strategies for AARS1-associated cancers.