Feline chronic gingivostomatitis (FCGS) is an inflammatory disease of the oral mucosa, affecting approximately 12% of domestic cats. Affected cats exhibit painful ulcerative and/or proliferative lesions throughout the oral cavity, leading to severe anorexia and weight loss. Surgical and immunosuppressive treatments are only partially effective. The etiology of FCGS remains unresolved, but it is thought to result from an abnormal immune response to oral antigens such as viral and bacterial infections. In aim 1, we will investigate genetic risk factors contributing to FCGS susceptibility through a genome-wide association study, using imputation to increase marker density to the whole genome level. In aim 2, we will characterize the transcriptome and epigenetic profiles of FCGS-affected compared to healthy feline oral mucosa tissues through single-nuclei RNAseq and assay for transposase-accessible chromatin with sequencing (ATAC-seq). Finally, we will elucidate the physical relationships among cell types in FCGS compared to normal tissue through spatial transcriptomics. This study will be the first to apply genotype imputation to feline SNP array data, which will not only be valuable for FCGS but will also improve association analysis of other complex diseases in cats. This work will, for the first time, characterize FCGS at the cellular level within the context of tissue architecture, informing our understanding of intercellular communication and cell-specific gene expression. These insights will enable us to propose a mechanism for how transcriptional and epigenetic alterations contribute to FCGS development, laying the groundwork for the identification of novel therapeutic targets.