Type II transmembrane serine proteases (TTSPs) are a growing family of multidomain proteins. Among the TTSPs, a new subfamily of HAT/DESC1-like ( human airway trypsin-like protease/ differentially expressed in squamous cell carcinoma gene 1) proteases is emerging consisting so far of four members: DESC1-3 and HAT. The cDNA of a new member of this subfamily, named DESC4, was isolated from rat tongue tissue and characterised. Analysis of selected tissues by RT-PCR demonstrated expression of DESC4 in brain, colon, heart, liver, lung and tongue. At the cellular level, DESC4 expression is confined to epithelial cells within the cleft of the circumvallate papillae extending into the ducts of minor salivary glands, the respiratory epithelium of the nasal cavity and tear gland ducts of the eyes as analysed by in situ hybridisation of sensory organ tissues. In transfected mammalian cells, DESC4 is localised to the plasma membrane as shown by immunocytochemistry and subcellular fractionation experiments. Our results suggest that we have identified a protease that is an important constituent of sensory systems and other organs.