ABSTRACT The United States Immunodeficiency Network (USIDNET) has been continuously funded as a resource for Clinical Immunologists since 1992, evolving from single diagnosis registries to a panel of research resources including a robust diverse patient registry with quality of life, laboratory, and clinical features; patient cell lines, and a variety of educational efforts. In 2017, the registry converted the data to SNOMED and LOINC terms, ushering in an era characterized by data standards and interoperability. The registry currently holds complex phenotype data on over 5000 patients with over 3000 discrete data fields. Genetic information is available on over 2000 patients. Under a new funding mechanism, USIDNET is poised to further enhance resources both incorporating and improving the state of genetic diagnostics for Inborn Errors of Immunity. Our central goal is to serve as a nexus of information on genotype and phenotype. The USIDNET registry will continue to serve a critical need by defining phenotypes and propelling improved outcomes research with enhanced longitudinal data. This evolution renders additional technical innovations possible in a manner that will serve community needs identified through discussion and a survey. This Program has six Aims which all derive from the central registry effort. The new registry will be anchored by a semi-automated data extraction from participating sites to maximize data standardization and longitudinal collection. Input of genetic data will be standardized and we will offer next generation sequencing to patients who otherwise cannot have sequencing, to improve the richness of genetic data in USIDNET and to nucleate a “matchmaking” effort. The six Aims are interwoven to support improved data and utilization. In Aim 1, we will improve the registry by developing a protocol for direct data extraction that can be shared across institutions and instituting a Single IRB to facilitate regulatory compliance. Aim 2 develops improved guidance for registry utilization, provides statistical support for end users, and spearheads studies of high impact, defined by the Steering Committee. Aim 3 proposes an innovative use of data to connect investigators who have similar patients through a specific matchmaking approach. In Aim 4, we will utilize USIDNET data to augment efforts to enrich immunology HPO terms and ClinGen entries. In Aim 5, we will galvanize successful dissemination efforts, develop a newsletter with structured features to improve clarity, and enhance material on our website. In Aim 6, we will formalize mentoring efforts to strengthen the research skills of the next generation and provide career mentoring. These resources will provide pivotal information for the Immunology community at a time when the wealth of new monogenic Inborn Errors of Immunity have made clinical decision making far more complex and uncertain. This new R24 builds on previous successes defining phenotypes in Inborn Errors of Imm...