(Pro)renin receptor (PRR), along with its soluble form, sPRR, functions not only as a crucial activator of the local renin-angiotensin system but also engages with and activates various angiotensin II-independent signaling pathways, thus playing complex and significant roles in numerous physiological and pathophysiological processes, including cardiovascular and metabolic disorders. This article reviews current knowledge on the intracellular partners of the PRR system and explores its physiological and pathophysiological impacts on cardiovascular diseases as well as conditions related to glucose and lipid metabolism, such as hypertension, heart disease, liver disease, diabetes, and diabetic complications. Targeting the PRR system could emerge as a promising therapeutic strategy for treating these conditions. Elevated levels of circulating sPRR might indicate the severity of these diseases, potentially serving as a biomarker for diagnosis and prognosis in clinical settings. A comprehensive understanding of the functions and regulatory mechanisms of the PRR system could facilitate the development of novel therapeutic approaches for the prevention and management of cardiovascular and metabolic diseases.