The Illinois Precision Medicine Consortium (IPMC) All of Us Research Program Site - The All of Us Research Program (AoURP) Illinois Precision Medicine Consortium (IPMC) award has created an impetus for precision health collaboration in Illinois that will leave a positive legacy for decades both locally and nationally. Since its inception, the IPMC has drawn strength from our institutional differences, varied scientific interests and expertise, broad geographic catchment areas, and different types of patient populations. To date, we have enrolled a cohort of nearly 52,000 participants from Chicago and greater Illinois, accounting for nearly 10% of the core AoURP participants nationwide – exceeding all expectations through high enrollment of informative research participants. Through the COVID-19 pandemic, the IPMC has proven that we can evolve and thrive in a new research context, pivoting operationally while ensuring project milestones. The experience of leading the AoURP in Illinois has generated insights, knowledge, best practices, new ideas, and partners to continue and build upon our work in Chicago and throughout Illinois. This includes a recognition of the crucial role that authentic and longstanding engagement plays in developing impactful biomedical research. We now have fully developed (and constantly expanding) clinical and community infrastructure, stakeholder buy-in, and integrated workflows. These will continue to guide IPMC performance and implementation strategies, supported by strategic investment and integrated expertise. We plan to continue enrollment and retention of participants into the AoURP by leveraging established leadership and frontline teams, infrastructure, workflows, and effective partnerships. We will work collectively to achieve the milestones outlined by the AoURP and implement the protocol fully and flexibly as national approaches, milestone priorities, and strategies and priorities evolve. To achieve these aims, the IPMC proposes to maintain our HPO institutional membership (University of Chicago, Northwestern University, University of Illinois Chicago) with Dr. Habibul Ahsan serving as the contact PI with MPIs Daviglus, Greenland, Aschebrook, Ho, and Pirzada. We are confident that our plan will bring significant value to the AoURP, with a precision medicine infrastructure based in Illinois that will ultimately enable discovery and impact communities we collectively serve and beyond.