This bill authorizes the Secretary of Health and Human Services, through the National Institutes of Health, to establish the INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE Project (INCLUDE Project) . This comprehensive program will conduct research, training, and investigation related to Down syndrome, aiming to advance scientific understanding and improve care. The INCLUDE Project will support high-risk basic science studies on chromosome 21's effects, expand clinical trials for novel interventions, and investigate biological mechanisms behind structural anomalies and cognitive dysfunction. It will also focus on identifying biomarkers for diagnosis and customized treatments, particularly for co-occurring conditions like Alzheimer's disease and autoimmunity, with the goal of improving the quality of life for individuals with Down syndrome. The bill mandates coordination among NIH institutes to prioritize non-duplicative research and requires biennial reports to Congress. These reports will detail research activities and any resulting real-world evidence, ensuring accountability and progress in this critical area of public health.