Hepatocyte growth factor activator inhibitor-2 prevents shedding of matriptase

► Matriptase, expressed alone, is rapidly transported though the secretory pathway and shed. ► Matriptase expressed together with HAI-1 and/or HAI-2 accumulates in the cells. ► Mutagenesis of Kunitz domain 1 but not Kunitz domain 2 abolished this function of HAI-2.