Prss21, also known as testisin, is a gene encoding a glycosyl-phosphatidylinositol-linked serine protease. It plays crucial roles in multiple biological processes. In the context of ovarian cancer, it is associated with tumor metastasis and angiogenesis-related pathways. In normal physiological conditions, it is important for sperm cell maturation and function [1,3].

In gene knockout studies, Prss21-deficient mice have shown significant phenotypes. In the ovarian intra-peritoneal tumor metastasis murine model, increased testisin expression inhibited intra-peritoneal tumor seeding, ascites accumulation, and metastatic tumor burden, with this function depending on its catalytic activity. Testisin was found to suppress the synthesis and secretion of pro-angiogenic angiopoietins ANG2 and ANGPTL4 by activating protease-activated receptor-2 (PAR-2) [1]. In the context of luteal angiogenesis, Prss21-deficient mice had increased vascular permeability and a hemorrhagic phenotype, with testisin identified as a novel regulator of VE-cadherin adhesions during angiogenesis [2]. In sperm-related studies, Prss21-deficient spermatozoa showed decreased motility, abnormal tail morphology, and impaired ability to respond to osmotic challenges, suggesting its importance in sperm maturation [3]. Mice lacking Prss21 and another sperm serine protease were subfertile, with mutant epididymal sperm unable to undergo acrosomal exocytosis and traverse the zona pellucida in vitro [4].

In conclusion, Prss21 is essential for both normal reproductive functions, especially sperm maturation and function, and in the context of ovarian cancer, it plays a role in regulating tumor metastasis and angiogenesis. Gene knockout mouse models have been instrumental in revealing these functions, providing valuable insights into the mechanisms underlying these biological processes and potentially suggesting new targets for treating related diseases such as ovarian cancer and male infertility.