This review systematically studies the molecular basis and regulatory mechanisms of LKB1-AMPK signaling in cardiovascular diseases-including atrial fibrillation, ventricular fibrillation, myocardial infarction, cardiac hypertrophy, heart failure, and atherosclerosis-where impaired pathway activity underlies energy deficits, fibrosis, oxidative stress, and arrhythmogenesis. This evidence concerns the gene STK11 and atrial fibrillation.