SPLUNC1 (short palate, lung, and nasal epithelial clone 1) is an epithelial-secreted protein implicated in innate immunity. SPLUNC1 has recently been identified as having a protective effect in lower respiratory inflammation and chronic rhinosinusitis (CRS). It has been hypothesized that a compromised epithelial immune barrier plays a crucial role in the development of CRS. Recent research has shown that SPLUNC1 is much lower in polyp tissues of CRS with nasal polyps compared to control tissues. There have been studies reported that look at the differential expression of SPLUNC1 in eosinophilic and noneosinophilic CRSwNP. Th2 cytokines reduced nasal SPLUNC1 expression, but toll-like receptor (TLR) agonists and glucocorticoids increased it. In CRS patients, decreased SPLUNC1 expression in the sinus mucosa is linked to positive Pseudomonas aeruginosa bacterial colonization and poor surgical results.

These results show that SPLUNC1 has a role in sinonasal innate immunity and the pathogenesis of CRS. Defective SPLUNC1 expression in CRSwNP patients may result in insufficient epithelial barrier function and increased bacterial colonization. The utilization of SPLUNC1 as a therapeutic target for CRSwNP is still being researched.