Notably, isoliquiritigenin was identified as a small-molecule inhibitor that targets the PITX1-PFKP axis, downregulating glycolysis and consequently suppressing breast cancer progression.<h4>Conclusion</h4>Our findings uncover a novel oncogenic mechanism by which PITX1 promotes breast cancer progression and metastasis through glycolytic reprogramming. Here, PFKP is linked to breast carcinoma.