Probing the familial ties between serpin members Kallistatin and PEDF: A comparative analysis review

The serine protease inhibitors (Serpins) represent a diverse protein superfamily that holds paramount significance in governing vital pathophysiological processes. Their influence on critical biological pathways renders serpins highly coveted targets for drug discovery endeavors. Among the numerous members of this family, two distinct proteins, Kallistatin (encoded by the SERPINA4 gene) and Pigment Epithelium-Derived Factor (PEDF, encoded by the SERPINF1 gene), stand out as secreted proteins that are abundantly present in peripheral blood. Kallistatin is a serine protease inhibitor that specifically inhibits human tissue kallikrein, while PEDF is a non-inhibitory member of the serine protease inhibitors superfamily (Lin et al., 2015a; Chao and Chao, 1995 [1,2]). Instead, they exhibit notable anti-angiogenic effects and play pivotal roles in the pathogenesis of metabolic disorders. Extensive research, including our own investigations, has revealed intriguing similarities as well as noteworthy differences between these two proteins. Despite their shared characteristics, the distinctive features of Kallistatin and PEDF render them unique in their respective functions and mechanisms of action. However, a comprehensive literature review comparing their similarities and differences remains elusive. Therefore, the present review aims to systematically delve into and summarize the comparable and contrasting aspects of Kallistatin and PEDF. We will delve into their expression patterns, structural features, and mechanisms of expression regulation. Furthermore, this review will delve into their physiological functions and roles in diseases, the signaling pathways they influence, and their potential clinical applications. By comparing and contrasting these two proteins, we hope to provide a comprehensive understanding of their functions and potential in biomedical research and clinical practice.