Progestogen-associated endometrial protein (PP14) (PAEP)

Progestogen-associated endometrial protein (PAEP), widely known as Glycodelin or Placental Protein 14 (PP14), is a 28 kDa secreted glycoprotein of the lipocalin family that serves as a critical immunomodulator and regulator of reproductive processes [2, 13]. It is primarily produced by the endometrial glands during the secretory phase and by the decidua during pregnancy, where it plays a vital role in creating an immunosuppressive environment that protects the semi-allogeneic fetus from maternal immune rejection [3, 11]. PAEP acts by binding to the tyrosine phosphatase receptor CD45 on T-cells, thereby inhibiting T-cell receptor signaling and inducing apoptosis in activated lymphocytes [8, 11]. In addition to its role in pregnancy, PAEP exhibits glycoform-dependent effects on fertilization, with different isoforms either inhibiting or stimulating sperm-oocyte interactions [5, 10]. Pathologically, its dysregulation is linked to infertility, endometriosis, and several malignancies—including breast and ovarian cancers—where it often promotes tumor immune evasion and progression [1, 10]. Clinically, it is utilized as a biomarker for endometrial receptivity and is indirectly targeted through hormonal therapies like progestins and progesterone antagonists that modulate its expression [6, 8].

Other names

GlycodelinPlacental protein 14PP14Progesterone-associated endometrial proteinPregnancy-associated endometrial alpha-2 globulinPEPPAEGZona-binding inhibitory factor-1ZIF-1Alpha uterine protein

Binding to CD45 to inhibit T-cell activation