Summary The overall mission of the San Diego Digestive Diseases Research Center (SDDRC) is to support basic, translational and clinical research that will lead to improved treatment and prevention of important inflammatory diseases of the gastrointestinal tract and liver. The foundation of our research efforts lies in a distinct group of academic investigators, carefully selected for Center membership based on the alignment of their work with the Center theme of "Inflammation in the Digestive Tract". The SDDRC provides Core services to the research groups of its members located at three adjacent research institutions in the San Diego area that foster research productivity and new research directions, and encourage productive collaborations. In addition, the SDDRC enhances new digestive diseases research through Pilot/Feasibility and Enrichment programs. The research base includes 45 outstanding and diverse investigators with current digestive diseases-relevant funding of $22,479,419 in total annual direct costs, of which $7,722,286 (34.4%) are from NIDDK. Since the SDDRC was originally funded by the NIH/NIDDK as Silvio O. Conte Center in 2019, the Center has experienced remarkable success. Over the past four years, 95% of all Center members have utilized Core services. The Center's exceptional productivity and impact are evident in the publication of 274 papers that are 100% compliant with NIH public access policy and acknowledge the Center grant in the publications based upon usage of SDDRC Core services. Collaboration among SDDRC members has played a pivotal role in driving this success, with ~50% of publications resulting from joint and collaborative projects between Center members. The Pilot/Feasibility program has supported 20 diverse and predominantly early-career investigators, who achieved an impressive success rate of ~80% in securing subsequent funding. Educational and training events organized by the Enrichment Core have been popular and well-received, as demonstrated by consistently high attendance rates and positive feedback. Building on these accomplishments, the SDDRC will continue to offer services to Center members through its three interrelated Biomedical Research Cores. The Human Translational Core leverages clinical and translational research expertise to offer access to human biospecimens, and provide consultation in biostatistics and histopathology. The Preclinical Models Core facilitates and assists in phenotyping and understanding of gastrointestinal and liver diseases using conventional and gnotobiotic murine models. The Microbiomics and Functional Genomics Core provides cutting-edge and cost-effective access to sequencing-based technologies and bioinformatic analysis. An Administrative Core supports the Center administratively and coordinates the Pilot/Feasibility and Enrichment programs. By creating a unique environment to nurture novel research ideas and interactions, the SDDRC is exceptionally well-positioned to inte...