CST11 (cystatin 11) is a cysteine protease inhibitor belonging to the family 2 cystatin superfamily, identified in the epididymis and expressed predominantly in the male reproductive tract 1. The protein is androgen-regulated and localized to the epididymal initial segment, throughout the epididymis, and on ejaculated human sperm 1. CST11 possesses dual biological functions: it demonstrates antimicrobial activity against Gram-negative bacteria, with recombinant CST11 reducing E. coli colony-forming units to 30% of control levels after 2-hour incubation 1. Additionally, CST11 belongs to the CRES (cystatin-related epididymal spermatogenic) subgroup, which may have evolved tissue-specific functions distinct from typical cystatins, suggesting roles in reproductive processes 2. Recent evidence indicates that CRES subgroup members, including related proteins, self-assemble into functional amyloid matrices in the epididymal lumen and associate with extracellular vesicles, potentially coordinating sperm maturation through interactions between luminal fluid and spermatozoa 3. These findings suggest CST11 functions both as a defense molecule against bacterial infection and as a component of reproductive tract homeostasis during sperm maturation and fertilization.