2024 Donald Seldin Lecture: New Insights Into Soluble (Pro)Renin Receptor in Hypertension and Kidney Disease

Also known as ATP6AP2, the PRR ([pro]renin receptor) was originally cloned over 2 decades ago as a component of the renin-angiotensin system due to its property of nonproteolytic activation of prorenin. After heated debates, this concept has been confirmed and expanded with advances in sPRR (soluble PRR) research. sPRR is a 28-kDa protein that is derived from the extracellular domain of PRR and is primarily released by site-1 protease. Circulating sPRR is elevated in patients with multiple diseases, including diabetes, hypertension, preeclampsia, and kidney disease. A decade ago, sPRR was found to have an antidiuretic function that occurs through the modulation of vasopressin signaling in the collecting duct. This finding signified the beginning of a new chapter in understanding the biological function of sPRR in multiple organ systems, particularly the kidney, and blood pressure regulation. In the past few years, numerous groundbreaking discoveries in this field have shed new light on the complex biology of sPRR, including its heterogeneity due to proteolysis and the multifaceted interaction between sPRR and the intrarenal renin-angiotensin system. The goal of this review is to summarize new advances in this emerging field of sPRR research.