The type II transmembrane serine proteases are divided into four phylogenetically distinct subfamilies: the human airway trypsin-like (HAT)/differentially expressed in squamous cell carcinoma gene (DESC) subfamily, hepsin/transmembrane protease serine (hepsin/TMPRSS) subfamily, matriptase subfamily, and the corin subfamily. This evidence concerns the gene HPN and squamous cell carcinoma.