The ORDRCC provides centralization of rheumatic disease research services through mentorship, clinical data, and biospecimens from ~71,000 patients registered in the managed collections of our Clinical Characterization and Biorepository Core (CCBC), comprised of comprehensive clinical evaluations linked to the only known rheumatic-disease-focused CAP-certified biorepository. To date we have granted investigator access to >103,000 samples and 4.2B data fields (clinical, experimental, immunologic, genetic). The 1,963 sample/data requests (571 in the past 4 years) have resulted in 445 publications and our 19 new investigator pilots have helped launch independent careers with their >$60M in external funding. CCBC- linked projects have achieved unique insights into disease processes, developed novel patient-reported outcomes and carried out innovative clinical trial designs, tailored for disease states with complex pathology. Autoimmune molecular phenotypes identified by our investigators are now being applied prospectively in NIH-funded and pharmaceutical trials, after identifying unique responder populations to targeted treatments that would have otherwise failed. The foundational goal of the CCBC is to help launch and support independent research careers by providing advisory clinical personnel and facilities otherwise inaccessible for many junior investigators and basic scientists. CCBC personnel have mentored or provided 151 IRB-approved study protocols, nearly all new JCI NIH Human Subject sections, patient recruitment (n=1,282), and more than 66,068 new sample aliquots linked to comprehensive clinical information. The current proposal responds to progress in advanced phenotyping science and evolving investigator needs by modeling clinical and translational research informatics and new methods for collecting and integrating molecular phenotype data with clinical and patient-reported data to facilitate precision medicine. We will continue to increase our collections in SLE, RA, UCTD, and Sjogren’s while adding new collections, including an autoantibody positive post-COVID cohort. Aim 1 will continue rheumatic disease clinical research support for ORDRCC Junior Investigators, Scholars, and Investigators with mentorship and regulatory assistance in clinical/interventional study design and a Clinical Research Service Unit for patient identification, recruitment, and clinical characterization. Aim 2 will expand and increase the sophistication of sample collection, management, SOPs, and Biorepository infrastructure, and support large rheumatic disease basic/clinical collaborations. In Aim 3 a new CCBC Innovation Hub will pilot new approaches for diverse patient recruitment, retention, characterization, home monitoring and remote sample collection to optimize real time access to patient samples and data as disease flares and improves. Aim 4 seeks to transform patient lives through science-driven clinical trial design that will reduce data complexity an...