Taken together, these results demonstrated that Irisin treatment inhibited VSMC glycolysis and thereby suppressed pyroptosis and medial calcification in the aortic tissues of CKD mice, whereas Fndc5 knockout promoted VSMCs glycolysis and pyroptotic cell death and exacerbated aortic medial calcification in CKD mice. The gene discussed is FNDC5; the disease is chronic kidney disease.