PROJECT SUMMARY/ABSTRACT Diabetes prevalence continues to rise globally, with more than 37 million individuals (11% of the population) currently affected in the United States. Approximately 15-20% of these people will experience a diabetic foot ulcer (DFU) at some point in their lives, with significant impact on quality of life, morbidity, and mortality. DFU are a harbinger of lower extremity amputation which occurs in approximately 150,000 Americans annually. Despite advances in wound care and related technologies, delayed healing and high recurrence rates of DFU remain major clinical challenges in current practice and create an enormous burden on patients and the healthcare system. In 2018 the NIDDK established the Diabetic Foot Consortium to address this large unmet need by execution of high quality, multi-center studies in DFU subjects with a focus on biomarker development and validation. The UCSF Diabetic Foot Clinical Research Unit (CRU) is one of the six initial participating centers in the DFC. Among its accomplishments, the DFC has executed two ongoing biomarker validation trials, initiated a biorepository protocol, reviewed multiple ancillary study proposals, and is currently finalizing a master protocol to enroll any patient with an incipient DFU. In its next renewal period, these DFC efforts will be expanded to include new candidate biomarkers, examine standard of care practices through a new master protocol, incorporate social determinants of health (SDOH), execute ancillary studies, and augment the recruitment of a diverse population by engagement of satellite sites. The UCSF Diabetic Foot CRU consists of two major affiliated medical centers- UCSF Medical Center and Zuckerberg San Francisco General Hospital- linked to satellite podiatry clinics in the Bay Area that share a research umbrella organization (Center for Clinical Research; CCR). Over the last year we have been able to expand subject recruitment for DFC trials dramatically by the incorporation of CCR clinics. We have also initiated pilot feasibility studies to incorporate SDOH collection within the currently ongoing biomarker trials (c- Myc and TEWL). During the next 5 year funding period, our multi-disciplinary research team will further contribute to the DFC by activation of a new common Master Protocol inclusive of all patients with an open DFU, incorporate the collection of SDOH data and examine its associations with outcomes, and expand the infrastructure through the addition of CCR clinical performance sites.