We hypothesize that feline calcivirus (FCV) plays an etiopathogenic role in feline chronic gingivostomatitis (FCGS). In this study we intend to assess the distribution and replication sites of FCV antigens and genome in cats with FCGS and assess the distribution and relative expression levels of feline junctional adhesion molecule A (fJAM-A) in oral tissues of affected and unaffected cats, using immunohistochemical and in situ hybridization techniques. Our findings will advance knowledge regarding of the etiopathogenesis of FCGS and may guide future therapeutic and investigative efforts. If we find that FCV is replicating in affected oral tissues of cats with FCGS, and that fJAM-A is exposed or dysregulated in affected cats, we will illustrate that the initial barrier dysfunction in FCGS is related to FCV infection, which in turn could allow other pathogenic or opportunistic microorganisms to access the underlying submucosal tissues. If our model is correct, a direct antiviral therapeutic may hold the greatest promise for cure. Recent development of highly specific calicivirus protease inhibitors might be one therapeutic avenue to consider under these circumstances.