Orphan granzymes find a home

Cytotoxic lymphocytes are armed with granules that are released in the granule-exocytosis pathway to kill tumor cells and virus-infected cells. Cytotoxic granules contain the pore-forming protein perforin and a family of structurally homologues serine proteases called granzymes. While perforin facilitates the entry of granzymes into a target cell, the latter initiate distinct apoptotic routes. Granzymes are also implicated in extracellular functions such as extracellular matrix degradation, immune regulation, and inflammation. The family of human granzymes consists of five members, of which granzyme A and B have been studied most extensively. Recently, elucidation of the specific characteristics of the other three human granzymes H, K, and M, also referred to as orphan granzymes, have started. In this review, we summarize and discuss what is currently known about the biology of the human orphan granzymes.