Serine protease 21 (Testisin) (PRSS21)

Serine protease 21, commonly known as testisin, is a glycosylphosphatidylinositol (GPI)-anchored serine protease primarily expressed in the testis and eosinophils [UniProt, NIH]. It plays a critical role in male fertility, specifically in the maturation and motility of spermatozoa, where its deficiency leads to structural defects such as "decapitated" sperm [NIH]. In addition to its reproductive functions, testisin is involved in extracellular signaling through the proteolytic activation of protease-activated receptor-2 (PAR-2) and the regulation of the urokinase-type plasminogen activator (uPA) system [PubMed]. In oncology, testisin is recognized as a cancer-testis antigen (CTA) that is aberrantly overexpressed in various malignancies, including ovarian and testicular cancers, as well as certain subtypes of acute myeloid leukemia (AMKL) [NIH, PubMed]. Its highly restricted normal tissue distribution makes it an attractive target for immunotherapy, including CAR-T cell therapies and engineered toxins designed for tumor-specific activation [PubMed]. Experimental strategies such as testisin-activated anthrax toxins (e.g., PrAg-PCIS) have shown efficacy in preclinical models by selectively targeting the proteolytic activity of the enzyme on cancer cells [PubMed].

Other names

TestisinEosinophil serine protease 1ESP-1Testicular serine protease 5TESP5Protease serine 21

Testisin acts by proteolytically cleaving and activating protease-activated receptor-2 (PAR-2) and pro-uPA on the cell surface, and it also interacts with the tumor suppressor maspin to modulate cell invasion and signaling pathways [PubMed, NIH].