Negative experiences and misunderstanding are common in tribalacademic research partnerships. The Holding Space: A Guide for Partners in Tribal Research draws on the concepts of governance, trust, and culture to strengthen relationships, honor tribal sovereignty, counter histories of opportunistic research, and recognize all ways of knowing. We apply the Holding Space toolkit concepts to the All of Us Research Program and call on all research studies funded by the federal government to honor governance, trust, and culture in research partnerships with tribal nations. Need for Tribal-Academic Partnerships While social and health research has addressed some health challenges in American Indian and Alaska Native (AI/AN) communities, 1,2 health disparities persist 3 and are not easily resolved. 2,4 For example, diabetes prevention and control require strategy implementation at the individual, family, and community level. 5 Additionally, many AI/ANs and tribal nations have long-standing mistrust of research and research policies shaped by interactions with opportunistic academic researchers doing federally funded work without tribal input or benefit sharing. 4,6,7 Participatory or community-engaged research is one approach to reducing mistrust and ensuring tribal communities' equal partnership in research. 8,9 Strong tribal-academic research partnerships that adhere to principles of participatory research can play a key role in developing the multilevel and contextualized solutions required to achieve health equity for AI/ANs. 9,10 The National Institutes of Health (NIH) and Patient-Centered Outcomes Research Institute acknowledge the scientific value of inclusive, partnered research, 11,12 and the Common Rule requires federally funded researchers to comply with state, local, and tribal laws. 13 However, theory-practice gaps-manifest in discounting tribal sovereignty, paying little attention to cultural protocols, or minimizing community concerns raised by research-can cause or reintroduce mistrust and exacerbate disparities. For example, one recent research incident with the Havasupai Tribe demonstrates the need for meaningful tribal-academic partnerships in genetics research. 14