BMPER (BMP binding endothelial regulator) is a secreted extracellular protein that functions as a BMP pathway inhibitor with diverse roles in vascular and skeletal development. Primary Function: BMPER regulates bone morphogenetic protein (BMP) signaling by binding BMPs and modulating their bioavailability. It acts as a positive regulator of angiogenesis and sprouting angiogenesis in endothelial cells 1, while also serving as a marker and positive modulator of adipogenesis in adipose tissue 2. Mechanism: BMPER suppresses BMP-induced SMAD1/5 phosphorylation and can modulate multiple signaling pathways including PI3K/AKT and YAP/LRP1 interactions in different cell types 13. During vascular remodeling, high fluid shear stress elevates KLF2-induced BMPER expression to suppress Smad1/5 and facilitate vessel outward remodeling 4. Disease Relevance: BMPER mutations cause diaphanospondylodysostosis (DSD), a rare skeletal dysplasia characterized by spinal and rib anomalies with variable phenotypic severity 5. BMPER dysregulation contributes to pulmonary arterial hypertension through excessive smooth muscle cell proliferation 13, and elevated BMPER is implicated in hemochromatosis via the SUGP2/CIRBP/BMPER axis regulating hepcidin expression 6. Clinical Significance: BMPER is essential for proper podocyte development and kidney structure maintenance 7, and therapeutic BMPER targeting shows promise for treating pulmonary hypertension and ischemic vascular disease.