SCUBE3 is a secreted glycoprotein that functions as a coreceptor for bone morphogenetic proteins (BMPs), particularly BMP2 and BMP4, facilitating their interactions with BMP type I receptors 1. It recruits BMP receptor complexes into lipid raft microdomains and positively modulates BMP signaling during chondrogenesis and osteogenesis. SCUBE3 also binds to and activates transforming growth factor-beta (TGF-β) signaling pathways. Loss-of-function variants in SCUBE3 cause a recognizable recessive developmental disorder characterized by reduced growth, craniofacial abnormalities, dental anomalies, and defective bone development 1. In healthy contexts, SCUBE3 is expressed in dermal papillae of growing hair follicles and promotes hair growth through TGF-β signaling 2, and promotes odontoblastic differentiation of dental mesenchymal stem cells 3. In cancer, SCUBE3 is pathologically upregulated and promotes tumor progression through multiple mechanisms. It supports cancer cell survival and therapy resistance by activating oncogenic signaling through EGFR, mutant CALR, and TGF-β receptors 4. SCUBE3 elevation in ovarian cancer correlates with unfavorable prognosis and drives progression via HIF-1 signaling 5. In lung cancer, SCUBE3 promotes angiogenesis and epithelial-mesenchymal transition 6. A first-in-class neutralizing antibody targeting SCUBE3 demonstrates therapeutic potential across multiple cancer types in preclinical models 4. Additionally, reduced SCUBE3 expression associates with systemic lupus erythematosus susceptibility 7.