1.1. ABSTRACT The first 7 years of 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. During the first 5 years of enrollment, the IPMC has drawn strength from our institutional differences, varied scientific interests and expertise, broad geographic catchment areas, and diverse patient populations. To date, we have enrolled a cohort of nearly 43,000 participants from Chicago and greater Illinois, accounting for nearly 10% of the core AoURP participants nationwide – exceeding all expectations for diversity through high enrollment (87%) of those underrepresented in biomedical research (UBR), despite a decreasing trend nationally. Through the COVID-19 pandemic, the IPMC has proven that we can evolve and thrive in a new research context, pivoting operationally while ensuring representation. This is important as the AoURP seeks new target populations (i.e., pediatric) and implementation approaches. 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 inclusive 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 intentional engagement investment and integrated expertise. We have identified new scientific partnerships at our Health Provider Organizations (HPOs) and MPIs, now including an additional minority serving institution (MSI) with significant UBR engagement expertise. The IPMC offers this proposal, to fulfill or exceed the AoURP requirements for OTA-22-006 Areas of Interest (AOIs). Under the direction of the AoURP and NIH, for AOI 1- Community, Participant and Provider Engagement, Enrollment and Retention, we will work with AoURP leadership and stakeholders nationally and IPMC-wide to engage and recruit a targeted 50,000 diverse core participants in Illinois during the 5-year award period. We plan to recruit at least 85% UBR into the AoURP by leveraging established leadership and frontline teams, infrastructure, workflows, and new engagement partnerships. We will work collectively to achieve the engagement, enrollment, and retention (active and passive) 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, NorthShore University HealthSystem, and Rush University, with subcontracts at University of Illinois Urbana-Champaign and University of Illinois Peoria) with Dr. Habibul Ahsan serving as the contact PI with MPIs Daviglus, Greenland, Aschebrook, Ho, Shah, Sanders, Pirzada, and Soares. We will also add a crucial engagement partnership with Governors State University, an MSI with Drs. Balthazar and Roberson joining as MPIs. Over the last 5 years, IPMC partners have demonstrated complementary reach into diverse patient populations while balancing key AoURP metrics (UBR engagement, high quality data, enrollment, and retention). We are confident that our 5-year plan will bring significant value to the AoURP, with an engaged and diverse participant population based in Illinois that will ultimately enable discovery and promote equity in the communities we collectively serve and beyond.