NK2 homeobox 5 (NKx2.5) is an earliest transcription factor related to the development and maturation of the heart, which may affect the abnormal development of the embryonic heart, and ultimately lead to the abnormal cardiac structure and conduction function, or even death. In this article, we review the biological characteristics of NKx2.5 and its mechanism of action in cardiac development, and introduce the newly discovered mutations in patients in recent years. The gene acts synergistically with other transcription factors during heart development to promote the development of precursor cardiomyocytes. Early detection of the gene will help to screen hereditary congenital heart disease and prevent sudden cardiac death caused by bradycardia or tachycardia.