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Lactylation, which serves as a key metabolic\u2010epigenetic bridge driving malignant progression, is involved in CRC development, metastasis, immunosuppression, and drug resistance. This review systematically outlines the biological functions of lactate and the molecular mechanisms of lactylation, with a particular focus on their regulatory roles in CRC. Key aspects are summarized, including the dynamic regulation by lactylation\u2010related enzymes (\u201cwriters\u201d and \u201cerasers\u201d) and potential therapeutic strategies targeting lactylation. Distinct from existing studies, this review further explores the clinical translational potential of targeting lactylation. From a toxicological perspective, it analyzes mechanisms of chemotherapy resistance and the toxicological considerations associated with targeted therapies. 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