Pregnancy zone protein (PZP) is an antiprotease-resistant immunosuppressant belonging to the α-macroglobulin (αM) protein family. PZP is secreted by the liver and was found to be upregulated in plasma during pregnancy. α-2-macroglobulin (Α2M) shares 71 % serial homology with PZP, but low PZP levels do not lead to increased A2M levels in pregnancy. PZP can interact with several factors such as low-density lipoprotein receptor-associated protein (LRP), transforming growth factor-β (TGF-β), 78 kDa glucose-regulated protein (GRP78), and glycoside A (GdA). PZP is involved in the development of glycolipid metabolism disorders, bronchiectasis, Alzheimer's disease (AD), rheumatoid arthritis (RA), myocardial infarction (MI) and inflammatory bowel disease (IBD). PZP is also associated with the progression of tumorigenesis such as breast cancer (BC), homologyepatocellular carcinoma (HCC), lung adenocarcinoma (LAC), and colorectal cancer (CRC). Therefore, this review analyzes the role of PZP in pathophysiology of various diseases.