In this Research Opportunity Announcement for Area of Interest 4, we describe the seminal work of establishing an infrastructure that operationalizes engagement of diverse research participants, distinct from recruitment/enrollment, and building on the foundational work of integrating research participants within the governance of research programs. Our approach and best practices are embedded into the Engagement Core’s five aims 1)Serve as the central hub for participant engagement – providing resources, expertise, and tools – to the All of Us Consortium for engaging participants as partners in the governance, priority setting, implementation, and evaluation of All of Us; 2) Effectively integrate participants, who reflect the broad diversity of All of Us, as partners in the governance, oversight, and evaluation of All of Us; 3) Capture and integrate the voices of diverse participants to enhance the design, implementation, and use of All of Us data, resources, and results; 4) Continuously assess the impact of participant engagement on all aspects and phases of All of Us including governance, design, implementation, and evaluation; and 5) Advance the science of engagement with an emphasis on engaging historically marginalized and minoritized groups. To date, our Engagement Core has established the infrastructure for participant engagement, by successfully integrating 81 participants (including 58 [72%] from minoritized and historically excluded communities into various All of Us governance roles including 12 members on the steering committee and 6 on the executive committee. Our Engagement Core has responded to 55 requests for engagement reflecting a range of activities including review of a mental health and well-being PPI survey and generating potential solutions to safely extend data access to non-traditional researchers in the All of Us Researcher Workbench. In the next phase, we will continue the multi-faceted strategies above and will expand our approaches to include voices currently missing from existing engagement such as young adults, and parents of children aged 18 and younger (critical given upcoming pediatric enrollment). We will also create new mechanisms such as a rapid feedback panels - a diverse group of participants who will provide time-sensitive feedback in critical areas. Ultimately, we will document successful strategies to contribute evidence-based recommendations for future large-scale studies with a substantial participant engagement component.