The All of Us Research Program has an explicit goal to enroll at least 1 million people from all communities to reflect the rich diversity of our nation. To truly engage our broad national diversity, a specific focus on sexual and gender minority (SGM) individuals is critical. Engaging SGM people will help ensure equitable representation of the US population in All of Us, biological heterogeneity for high-quality discovery science, and diverse input in All of Us-based research via citizen-scientists and traditional researchers. Our proposal aims to engage SGM people on a national scale to help the All of Us Research Program realize its ambitious goals. SGM people – including members of the lesbian, gay, bisexual, transgender, and queer (LGBTQ) communities – are everywhere, demographically diverse, and represent all segments of society. SGM people account for an estimated 4.1% (~13 million people) of the US population. SGM individuals compose an identity-based population that includes sexual minorities (individuals with a sexual orientation that is not heterosexual) and gender minorities (individuals with a gender identity that is not congruent with their sex assigned at birth). SGM communities share a common experience of social marginalization, legal discrimination, political disenfranchisement, and familial rejection. Despite limited data, SGM people are believed to live in nearly all counties in the United States, be a part of other underrepresented minority groups, be in every socioeconomic stratum, and speak the diversity of languages in our nation. To examine this, we recently analyzed all the last three years (2013-2015) of National Health Interview Survey (NHIS) data (manuscript under review) and found that self-identified lesbian, gay, and bisexual people were primarily younger (28% were 18-29 years old, 17% were 30-39, 20% were 40-49, 26% were 50-64, and 9% were 65 years or older). Approximately 14% were of Hispanic ethnicity. Regarding race, 80% were Caucasian, 15% were African/African-American, and 5% were another race. Approximately 30% reported an annual earned income of $0 while 11% reported earning more than $75,000. SGM people are largely invisible in federal population-based efforts because they are not counted. Because sexual orientation and gender identity are not collected during the decennial US Census, the precise number of SGM people in the US as well as their age, geographic, linguistic, race, ethnicity, income, and regional distributions are unknown. Without these data, national population-based studies (e.g., National Health and Nutrition Examination Survey, NHANES) are unable to generate sampling frames that adequately account for the disproportionate geographic distribution of SGM people (e.g., San Francisco city census reports that ~15% identify as SGM). In 2010, the NIH commissioned the Institute of Medicine (now National Academy of Medicine) to study SGM health to inform the nation’s SGM health research agenda. In addition to recommending research in nearly all aspects of health, the consensus committee poignantly stated, “[t]he relative lack of population-based data presents the greatest challenge to describing the health status and health-related needs of LGBT people” and emphasized the need for national research efforts, such as All of Us, to explicitly include data measures or questions about SGM identity. This report and other research led the National Center for Health Statistics to include sexual orientation in the NHIS and the NIH to designate the SGM population as a “health disparity population for research purposes” in October 2016. SGM people are an underserved and understudied population that is vulnerable to poor health. SGM people experience unique health and healthcare disparities including higher rates of smoking, HIV infection, certain cancers, depression, suicide attempts, and delaying access to health care. Infrequent collection of sexual orientation and gender identity data in clinical settings makes performing SGM-specific studies challenging. Healthcare providers receive inadequate training in caring for SGM patients that often results in mistreatment or discrimination, which deters research participation. While these inequities have been associated with societal stigmatization and minority stress in small studies, difficulties identifying and studying SGM communities severely hinder the identification of health disparity etiologies and the design of appropriate interventions. By meaningfully including and engaging SGM people, the All of Us Research Program has the potential to have a tremendous impact the health and well-being of millions.