PRSS21 (serine protease 21), located on chromosome 16.3, encodes testisin, a glycosylphosphatidylinositol-anchored serine protease with diverse physiological roles. Primary function: PRSS21 regulates proteolytic events in testicular germ cell maturation and epididymal sperm development 1. The protein is abundantly expressed in spermatozoa and microvascular endothelial cells 2. Mechanism: Testisin acts as a membrane-anchored protease that activates protease-activated receptor-2 (PAR-2) to regulate angiogenic processes and cell adhesion 3. During sperm maturation, PRSS21 deficiency causes decreased motility, tail abnormalities, and increased sperm fragility 4. In endothelial cells, testisin maintains vascular integrity by preserving VE-cadherin expression and reducing vascular permeability during angiogenesis 2. Disease relevance: PRSS21 shows aberrant methylation in testicular germ cell tumors and is differentially expressed in ovarian metastatic carcinomas 53. Testisin expression suppresses ovarian tumor metastasis and ascites accumulation by antagonizing pro-angiogenic angiopoietins ANG2 and ANGPTL4 3. Clinical significance: PRSS21 dysregulation may underlie male infertility syndromes and testicular pathologies, while representing a potential therapeutic target for controlling tumor angiogenesis and metastasis 46.