PRSS22 (serine protease 22) is a trypsin-like serine protease that functions as an enzymatically active endopeptidase with distinct substrate preferences compared to other family members 1. The enzyme is constitutively secreted from epithelial cells and shows developmentally regulated expression patterns, being highly expressed in trachea, esophagus, and fetal lung tissues 1. PRSS22 promotes cancer progression through multiple mechanisms, including cleavage of ANXA1 protein to activate FPR2/ERK signaling pathways that enhance breast cancer metastasis 2. In colorectal cancer, PRSS22 inhibits HMOX1-mediated ferroptosis and cleaves osteopontin to promote M2 macrophage polarization, thereby facilitating colitis-associated carcinogenesis 3. Pan-cancer analyses reveal that PRSS22 expression shows significant cancer-type specificity and is associated with worse overall survival in multiple cancer types including kidney, liver, lung, and skin cancers 4. The protease also influences the tumor immune microenvironment and demonstrates context-dependent roles across different malignancies 4. Additionally, PRSS22 expression and methylation patterns are associated with maternal iron status during pregnancy and Ascaris exposure, suggesting roles in developmental and environmental responses 56.