Pzp, also known as Pregnancy zone protein, is a multifunctional protein belonging to the proteinase inhibitor I39 (α -2 -macroglobulin) family [1,3]. It was originally identified as a protease inhibitor, but current evidence suggests it may function as a modulator of T -helper cells and/or an extracellular chaperone [1]. Pzp is elevated in normal pregnancy and numerous inflammatory states, and is implicated in extracellular proteostasis and immunoregulation, which are crucial for a variety of biological processes [1].

Reduced levels of Pzp are associated with preeclampsia, a leading cause of maternal and foetal mortality and morbidity [1]. A GWAS analysis found novel risk loci in the proximity of Pzp, indicating its involvement in the development of placenta, remodeling of uterine spiral arteries, kidney function, and maintenance of proteostasis in pregnancy serum [2]. Pzp expression was significantly downregulated in the syncytiotrophoblast and extravillous trophoblast of preeclampsia and HELLP syndrome patients, suggesting its role in the development of placental dysfunction in these disorders [4]. In hepatocellular carcinoma, the gene encoding Pzp is hypermethylated and expressed at low levels, and Pzp markedly inhibits the proliferation, invasion and migration of HCC cells [3].

In conclusion, Pzp plays important roles in pregnancy-related physiological processes and is closely associated with diseases like preeclampsia and hepatocellular carcinoma. The study of Pzp helps to further understand the mechanisms of pregnancy-related disorders and tumorigenesis, potentially providing new insights for disease treatment and prevention.