Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition arising from germ line mutations in the Folliculin (Flcn) gene that cause mis-folding or truncation of the protein. Although the biological function of Flcn is not fully known its mutation effects are diverse, causing skin fibrofolliculoma, renal cancer, lung cysts and pneumothorax. Research into the lung-based aspects of BHD is hampered by the lack of suitable culture models and the risk of pneumothorax prevents collection of airway biopsy material. Human nasal epithelial (HNE) cell culture offers a solution as its collection avoids sites of lung pathology and yields viable epithelial tissue. The first purpose of this study (Part 1) was therefore to establish proof-of-principle for this model by determining if HNE cells express Flcn and its interacting partner, FNIP-1. Lung cyst formation has been linked to elevated matrix-metalloproteinase-9 (MMP-9) activity (Pimenta et al., 2011) which disrupts epithelial turnover, therefore, our second purpose was to determine if MMP-9 inhibition recovers growth of human bronchial epithelial (HBE) cells carrying a stable knockdown of the Flcn gene (Part 2). For Part 1, HNE cells were obtained from four consenting donors by rubbing a cytology brush against the inferior turbinate. Cell material was cultured in Basal Epithelial Growth Medium and used for immunofluorescence and qPCR. For Part 2, HBE cells (16HBE14o-) stably transformed with either non-genomic or Flcn shRNA were treated with the MMP-9 inhibitor, Ilomastat (10μM), and ERK1/2 and retinoblastoma protein (Rb) phosphorylation were assessed to determine the effect on growth signalling pathways. Results for Part 1 demonstrated that mRNA and protein for Flcn and FNIP-1 were expressed in both ciliated HNE and also HBE cells. In HNE, immunofluorescence revealed that Flcn/FNIP1 localised to the ciliary base plate region and were associated with the ciliary markers, pericentrin and acetylated tubulin. Thus, Flcn/FNIP1 are apically polarised in HNE, suggesting that these cells are suitable for exploring Flcn function in airway epithelial organisation. Results for Part 2 revealed that Flcn knockdown in HBE attenuated cell growth (decreased S807/811 phosphorylation of Rb) relative to controls and that Ilomastat recovered this effect, together with elevated ERK1/2 T202/Y204 phosphorylation (n=4). Thus, an MMP-9-sensitive mechanism suppresses cell cycle activity in Flcn knockdown HBE cells, a phenomenon which could contribute to cyst formation in the BHD lung. Taking both parts of this study together, we conclude that Flcn and its partner protein, FNIP1, are expressed in airway epithelium and participate in the regulation of cell polarity and proliferation.