Rhomboid protease is a transmembranal serine protease. The active site is buried in the lipid bilayer of cell membrane. It cleaves proteins within their transmembrane domain. Rhomboids regulate many cellular processes and are involved in many human diseases. The catalytic site of rhomboids contains a hydrophilic pocket protected by from the lipid bilayer. Rhomboids are specific for a single transmembranal helix proteins.