APLN (apelin) is an X-linked adipokine that functions as the endogenous ligand for the apelin receptor (APLNR), a G protein-coupled receptor with pleiotropic physiological roles 1. Primary functions include regulation of vascular development, blood pressure homeostasis, and reproductive processes. APLN activates APLNR signaling through AKT and MAPK3/1 pathways 2, promoting vascular endothelial cell proliferation and angiogenesis while suppressing smooth muscle cell proliferation 3. APLN+ tip cells mark early angiogenic stages in tumor vasculature and predict poor prognosis and anti-VEGF therapy response 3. In reproduction, APLN maintains blood-testis barrier integrity through cell adhesion gene expression; hyperactivation of the APLN/APJ axis in diabetes impairs spermatogenesis, which can be rescued using APLNR antagonist ML221 4. In female reproduction, APLN enhances granulosa cell steroidogenesis and is dysregulated in polycystic ovary syndrome 2. Clinically, reduced serum apelin-13 correlates with preeclampsia severity and hypertension 5. APLN also modulates immune responses through macrophage regulation during cardiovascular disease 6. These findings identify the APLN/APJ axis as a therapeutic target for metabolic, cardiovascular, and reproductive disorders.