• Lactylation of MLKL at K230 is elevated in breast tumor stem cells and promotes their stemness.
• K230R mutation of MLKL reduces cell migration, spheroid formation, and alters EMT marker expression.
• MLKL lactylation at K230 enhances epithelial-mesenchymal transition, contributing to tumor progression.
• Targeting MLKL K230 lactylation may represent a novel therapeutic strategy for breast cancer.
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