High-temperature requirement factor A3 (HtrA3) is a serine protease, which has been identified as an important target molecule in diseases such as cancer and pregnancy complications. The regulatory role of this molecule is attributed to its extensive biological functions. However, there is still a lack of effective integration regarding this aspect. Therefore, in this article, we discuss the biological functions of HtrA3,including its involvement in protein quality control, immune regulation,maintenance of mitochondrial homeostasis,apoptosis,extracellular matrix degradation, and epithelial-mesenchymal transformation, as well as its role in regulating cell proliferation and migration. In addition, studies have confirmed that HtrA3 is predominantly expressed in the heart, with significant research progress made regarding this molecule in the contexts of myocardial fibrosis, heart failure, and ischemia-reperfusion injury. Given its extensive functions, HtrA3 may serve as a significant regulator of cardiovascular diseases, highlighting its important research value in the development of cardiovascular diseases.