Literature search was conducted in PubMed and Google Scholar by using a combination of keywords as follows: “activating transcription factor 4′′OR “ATF4′′, “integrated stress response” OR “ISR”, “cardiovascular disease” OR “heart disease” OR “coronary heart disease” OR “cardiomyopathy” OR “heart failure” OR “cardiovascular aging” OR “atrial fibrillation” OR “calcific aortic valvular disease” OR “vascular calcification”. The gene discussed is TCF4; the disease is cardiovascular disorder.