PAPPA (pappalysin 1) is a zinc-dependent metalloproteinase located on chromosome 9.1 that specifically cleaves insulin-like growth factor binding proteins (IGFBP-4 and IGFBP-5), thereby releasing bioactive IGF-1 and IGF-2 1. The enzyme's activity is enhanced by IGF presence during IGFBP-4 cleavage but slightly inhibited during IGFBP-5 cleavage. PAPPA is expressed in ovaries, endometrium, placenta, and other tissues, where it regulates localized IGF signaling 1. In female reproduction, PAPPA peaks in dominant ovarian follicles before ovulation in response to gonadotropins, promoting follicular growth and steroidogenesis 1. PAPPA is essential for normal fetal development, placental function, and endometrial receptivity; PAPPA-null mice show reduced body weight and bone density 1. Clinically, PAPPA serves as a biomarker for oocyte and embryo quality in in vitro fertilization, fetal aneuploidies, and ectopic pregnancies 1. Beyond reproduction, PAPPA plays pathological roles in polycystic kidney disease through excessive IGF-1 pathway activation 2, and in atherosclerosis where dysregulation via the MIAT/miR-148b and circ-CHFR/miR-214-3p axes promotes vascular smooth muscle cell proliferation and migration 34. PAPPA also contributes to cellular senescence through sirtuin-regulated chr9 remodeling 5.