IGFBP4 is an insulin-like growth factor binding protein that modulates IGF signaling through multiple mechanisms. Structurally, IGFBP4 prolongs IGF half-life and alters IGF interactions with cell surface receptors, thereby regulating growth-promoting effects 1. The IGFBP4 gene is regulated by transcription factors including Sp3 and AP-1, with cAMP signaling enhancing promoter activity 21. IGFBP4 functions as an inhibitor of IGF action in bone tissue and participates in negative regulation of Wnt signaling 23. Clinically, IGFBP4 has emerged as a biomarker and therapeutic target across multiple diseases. In diabetic kidney disease, elevated IGFBP2/IGFBP4 interact to activate complement pathway activation in macrophages, promoting podocyte apoptosis 4. IGFBP4 serves as an independent prognostic factor for chr17 lymphocytic leukemia, with high expression correlating with poor survival 5. In autosomal dominant polycystic kidney disease, PAPP-A-mediated cleavage of IGFBP4 increases local IGF-1 bioavailability and promotes cyst growth; blocking PAPP-A proteolytic activity against IGFBP4 ameliorates disease progression 6. In Crohn's disease, IGFBP4 produced by placental mesenchymal stromal cells activates AMPK-FXR pathway signaling to reduce intestinal inflammation and restore barrier function 7. IGFBP4 also suppresses ferroptosis in bone metabolism, promoting osteogenic differentiation crucial for fracture healing in idiopathic osteoporosis 8.