The Model Systems Core continues the Pittsburgh Center for Kidney Research’s rich history of using creative approaches to drive the latest conceptual advances in kidney physiology and pathophysiology. The goal of this biomedical resource Core is to provide a diverse array of innovative model systems that will allow kidney researchers to explore renal development, function, and systemic physiology in normal and disease states. The Core is divided into three Subcores that extend from simple unicellular organisms to complex whole animal models. Taking advantage of the genetically tractable organism S. cerevisiae, the Yeast Models Subcore provides a toolbox for the analysis of conserved genes that play essential roles in kidney physiology and proteostasis. The Epithelial Models Subcore provides access to high fidelity immortalized proximal and distal tubule cell lines, primary cell isolations, and state-of-the art human kidney organoids for the development of disease models, analysis of nephron development, metabolism, function, and response to injury. The Animal Models Subcore provides a broad repertoire of methods to evaluate rodent kidney physiology and pathophysiology, associated cardiovascular variables, mitochondrial health and bioenergetics, and purine metabolomics. Using an infrastructure supported by its established investigators and record of productivity, the Model Systems Core will work seamlessly with the Physiology Core and the KIDNIT Resource Development Core to facilitate discovery. As part of the Consortium, the Core will ensure a facile exchange of tools, technologies, and specialized Center resources to advance kidney research nationwide. Accordingly, the Core welcomes all collaborators, offers mechanisms to promote Subcore tools and reagents, provides hands-on instruction (i.e., mini-sabbaticals), and will facilitate collaborative resource sharing with individual investigators as well as with the Consortium at large. For early-stage investigators and established PIs who are new to kidney research, key resources, training, and collaborative opportunities will be prioritized to cultivate enthusiasm and entry into an active research pipeline. The Core will also provide expert advice and aid in the acquisition of preliminary data to support new and innovative grant applications. Stringent quality control measures will ensure the rigor and reproducibility of Subcore outputs, and a formalized evaluation and feedback process permits regular reassessment of the usefulness of Core resources. By offering impactful state-of-the-art and readily accessible services across diverse model systems, the Core will provide a unique national resource for the kidney research community that will propel team-based investigation and catalyze discovery.