Biological functions of FASN in tumor lipid metabolism and research advances in its covalent modifications.

De novo lipogenesis (DNL) operates as a core metabolic pathway in cellular lipid homeostasis, yet its central effector enzyme fatty acid synthase (FASN) undergoes aberrant overexpression and hyperactivation in tumors and metabolic disorders. Herein, we systematically outline the versatile functions of FASN in tumor lipogenic metabolism and summarize recent advances in its covalent regulatory modifications. We highlight nucleic acids methylation modifications, acetylation, ubiquitination, glycosylation, ubiquitin-like modification, palmitoylation and phosphorylation modifications as an integrated network that tune FASN stability, catalytic activity, and subcellular localization. These modifications exhibit extensive crosstalk and disease-specific heterogeneity, offering potential molecular targets for therapeutic intervention in cancer and metabolic diseases.