PROJECT SUMMARY The renin angiotensin aldosterone system (RAAS) is a key regulator of cardiovascular (CV) function, fluid electrolyte balance, and homeostasis, and it influences many systems including the renal, neuroendocrine, and immune systems. Perturbations of the RAAS trigger a cascade of events, including generation of vasoactive mediators, oxidative stress, inflammatory responses, and tissue remodeling, thus contributing to end-organ pathology and disease. In the 2022 GRC on Ang, we will discuss the most recent, cutting-edge discoveries in the field and share insights on emerging new areas beyond the CV system such as the role of the RAAS in adipose biology, bone marrow regulation, liver function, neurocognition, and immune responses. The conference will focus on the latest advances of the RAAS from discovery science to clinical impact. A highlight in 2022 will be the celebration of 22 years of the discovery of ACE2. ACE2 is a multifunctional protein, that not only is CV protective by generating Ang-(1-7) and Ang-(1-9) from Ang II and Ang I respectively, but it is also, tissue injurious by acting as the receptor for the SARS-CoV-2, the etiologic agent of the current worldwide COVID-19 pandemic. The enigmas of ACE2 as a key enzyme in the protective arm of the RAAS will be a highlight. The role of ACE2 as a major mediator and potential therapeutic target in COVID-19 will be debated along with the controversies on the progression of COVID-19 infection and long-term outcomes in populations treated with ACE inhibitors and/or angiotensin receptor blockers. The 2022 GRC on Ang will further feature novel topics including sex-differences in the regulation and changes of the RAAS during the life course (fetal programming, kidney development, and aging) will be further addressed. In line with precision medicine being the next frontier in clinical medicine, the meeting will also highlight new advances in the pharmacogenomics, proteomics, and metabolomics of the RAAS in human diseases. Preceding the GRC, we will have the 2022 Gordon Research Seminar (GRS), a special forum for graduate students, postdoctoral fellows, early career researchers and other junior scientists to present and exchange new data and cutting-edge ideas. The 2022 GRS will focus on recent advances in RAAS studies beyond the classical paradigms, including new functions of receptors from this system and providing trainees with an enhanced understanding of current tools to aid their research, and cover a wide range of topics including the immune system, sex differences and aging. Additionally, the mentorship sessions will address the interplay between academia and industry and discuss approaches to translate scientific discoveries to the clinic and how to optimize impact. The aims are aligned with the NHLBI, NIDDK and NIAID missions and initiative and the scientific themes that will be covered are of direct relevance to these institutes. NIH funds requested will help attract young inves...