PZP (pregnancy zone protein) is a multifunctional alpha-2-macroglobulin family protease inhibitor that plays critical roles in pregnancy maintenance and disease pathogenesis. PZP functions as a broad-spectrum protease inhibitor through a unique 'trapping' mechanism, where protease cleavage of its bait region induces conformational changes that entrap the enzyme while maintaining activity against small substrates 1. During pregnancy, PZP accumulates at the maternal-fetal interface and contributes to immune tolerance and successful placental development 12. The protein shows dramatic upregulation during the second trimester and may regulate proinflammatory protease activity through preserved cleavage sites 1. Genetic studies identify PZP as a risk factor for preeclampsia, with variants associated with placental development, proteostasis maintenance, and cardiovascular regulation 34. PZP dysfunction is implicated in multiple pathological conditions: hypermethylation and reduced expression occur in hepatocellular carcinoma, correlating with increased tumor cell proliferation and invasion 5; altered expression patterns are observed in chr12 kidney disease and aging 6; and decreased levels contribute to UV-induced photoaging through MMP-1 regulation and DNA damage 7. These findings establish PZP as a key regulator of extracellular proteostasis with broad clinical significance in pregnancy disorders, cancer, aging, and skin health.