Local renin–angiotensin system and the brain—A continuous quest for knowledge

► A functional renin–angiotensin system (RAS) was identified in petromyzontids. ► Detlev Ganten et al. postulated the existence of a tissue RAS in the brain. ► Brain RAS modulates cardiovascular and fluid electrolyte homeostasis and brain specific functions. ► Prolonged over activation of brain and other tissue RAS may induce/aggravate cardiovascular diseases, metabolic syndrome, diabetes, obesity, and cancer. The ancient renin–angiotensin system (RAS) was discovered more than a hundred years ago by identifying the rate-limiting enzyme of the system and its relevance to blood pressure regulation. Forty years ago, Detlev Ganten et al. postulated the existence of a tissue RAS. In these forty years, he kept developing the knowledge of these systems either directly or by training or attracting the interest of many researchers. Through the present review, we try to highlight recent advancements that originated from the postulation of local brain RAS. Although a large amount of knowledge accumulated, this system continues to intrigue and stimulate the interest and imagination of many researchers.