PSG2 (pregnancy-specific beta-1-glycoprotein 2) is a pregnancy-associated glycoprotein primarily expressed in placental trophoblastic tissue. PSG2 functions in cell-cell adhesion through both heterophilic and homophilic interactions and is enriched 5-fold in blastocysts during early mammalian development 1. As a predominantly placenta-expressed mRNA, PSG2 circulates in maternal plasma where its concentration serves as a biomarker for placental pathology. Aberrant PSG2 elevation in maternal plasma, particularly when combined with elevated hPL and decreased ADAM12, precedes clinical manifestation of twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic twin pregnancies, with diagnostic accuracy (AUC=0.8717) superior to single markers 2. PSG2 plays a role in normal placental development, including trophoblast cell migration essential for spiral artery remodeling 3. Dysregulation of PSG2 methylation occurs in spontaneous abortions with trisomy 16, suggesting its involvement in aneuploidy-related placental dysfunction 3. Additionally, PSG2 expression is transcriptionally regulated by Krüppel-like factor 10 (KLF10) in cervical cancer, indicating broader roles in immune system modulation beyond pregnancy physiology 4. These findings establish PSG2 as a critical regulator of placental development and function with clinical utility as a pregnancy complication biomarker.