• KIF5A is highly expressed in LUAD and correlates with glycolysis-related genes, promoting docetaxel resistance.
• Silencing KIF5A inhibits glycolysis, lactate production, and DTX resistance in LUAD cells.
• FOXP3 transcriptionally activates KIF5A, and its knockdown reduces lactate production and enhances DTX sensitivity.
• The FOXP3-KIF5A-lactic acid axis offers a novel therapeutic target to improve chemosensitivity in LUAD.