Hepsin: a multifunctional transmembrane serine protease in pathobiology.

Li, Shuo; Wang, Lina; Sun, Shijin; Wu, Qingyu

Cell membrane-bound serine proteases are important in the maintenance of physiological homeostasis. Hepsin is a type II transmembrane serine protease highly expressed in the liver. Recent studies indicate that hepsin activates pro-hepatocyte growth factor in the liver to enhance Met signaling, thereby regulating glucose, lipid and protein metabolism. In addition, hepsin functions in non-hepatic tissues, including the adipose tissue, kidney, and inner ear, to regulate adipocyte differentiation, urinary protein processing, and auditory function, respectively. In mouse models, hepsin deficiency lowers blood glucose, lipid and protein levels, impairs uromodulin assembly in renal epithelial cells, and causes hearing loss. Elevated hepsin expression has also been found in many cancers. As a type II transmembrane protease, cell surface expression and zymogen activation are essential for hepsin activity. In this review, we discuss the current knowledge regarding hepsin biosynthesis, activation, and functions in pathobiology.