SCUBE1 (signal peptide, CUB domain and EGF-like domain containing 1) is a secreted protein with multifaceted roles in vascular biology and tissue repair. As a BMP co-receptor, SCUBE1 enhances bone morphogenetic protein signaling, particularly BMP7-mediated renal protection following ischemia-reperfusion injury 1. The protein functions as an adhesive molecule stored in platelet alpha-granules and translocated to the surface upon stimulation, where its matrix-bound and soluble fragments support platelet adhesion and vascular homeostasis 2. Beyond hemostasis, SCUBE1 plays critical roles in pathological conditions: cancer-associated fibroblasts secrete SCUBE1 to promote hepatocellular carcinoma malignancy and stemness through Shh/Gli1 pathway activation 3, while elevated SCUBE1 levels independently predict thrombotic complications and mortality in COVID-19 patients 4. Recent machine learning analysis identified SCUBE1 as a key gene in diabetic foot ulcers, where it regulates immune responses in macrophages and NK cells 5. Additionally, SCUBE1 appears as a causal factor in endometrial cancer pathogenesis through protein-metabolite interactions 6, and MR antagonism downregulates SCUBE1 to improve corneal integrity in limbal stem cell deficiency 7. These findings establish SCUBE1 as a pleiotropic therapeutic target with diagnostic potential across cardiovascular, metabolic, and malignant diseases.