Human protease-activated receptor 2 (PAR2) is one of 4 members in a unique subclass of the Class A G protein- coupled receptor superfamily. Receptor activation involves the proteolytic uncovering of a cryptic N-terminus receptor sequence that forms a tethered ligand and binds to the receptors within the extracellular loop 2. This activates the receptors to initiate multiple signaling cascades. In addition, short peptides (5-6 amino acids) synthesized based on the proteolytically revealed motif can activate the receptors without the cleavage by enzymes. PAR2 is activated by trypsin and trypsin-like enzymes, and the cleavage site has been identified at residue Arg 36. PAR2 plays an important role in the regulation of cardiovascular, gastrointestinal, and skin function. PAR2 is expressed in human vascular tissues, pancreas, kidney, colon, liver, small intestine, and some tumor cell lines (1, 2).