Summary/Abstract: The Lymphatic Forum 2021 (LF2021) will be the 3rd iteration of a planned conference series that bring together researchers from around the world that study lymphatics in health and disease. The lymphatic system is a relatively understudied, yet vital component of the cardiovascular system that couples the tissue parenchyma to the venous blood via lymph flow through a complex network of lymphatic vessels. It transports fluid, macromolecules, lipids, tissue catabolic products and immune cells/agents as lymph. Thus, the lymphatic system provides critical links for the transport of fluid, macromolecules, cells and other elements from the interstitial space of all organs to and through numerous lymph nodes to the venous blood. In completing this transport, it regulates body fluid volume, macromolecular homeostasis, immune function, inflammation and lipid absorption/metabolism. It is a specialized vascular system with a complex network of low-pressure vessels with unique mechanisms to form and transport lymph. The lymphatic system serves as both a complex network of lymph conduits and as a series of unique intrinsic lymph pumps that generate and regulate the lymph flow that drives all of its functions. Because of its unique, complex structural and functional characteristics, it has been difficult to examine and quantify its structure and function in the body. However, a better understanding of its structure and function is important to health and disease. Other international/national lymphatic biology conferences, including the previous Lymphatic Forum 2017 and 2019 focused predominantly on the embryologic development, lymphangiogenesis, lymphatic endothelial cell function and relationships to cancer and immunity. The conference plan outlined in this application is unique in that it is the first to address the significant role and functions of the lymphatic vascular system in the various organs of the human body. Accordingly, the Forum’s program is designed to pay particular attention to the complex aspects of the lymphatic vascular system in the normal function of, and pathologies associated with, these organs. Presentations and discussions will focus on the molecular regulation of lymphatic development in a specific organ, the description of organ diseases and the known or suggested lymphatic dysfunctions and/or immune dysregulations in that organ that could explain or contribute to the disease and its development. The lymphatic system is an intrinsic, understudied part of the cardiovascular and the immune systems that influences health and disease. The goal of LF2021 is thus highly relevant to the missions of the NHLBI which has accepted primary assignment on this application, but also of the NIDDK and the NIAID, which will be asked for secondary support. Additionally, the conference is specifically designed such that trainees and young investigators have significant roles.