TWSG1 (Twisted Gastrulation BMP Signaling Modulator 1) is a secreted glycoprotein that functions as a dual regulator of BMP signaling during development and disease. Structurally, TWSG1 contains two disulfide-rich domains that enable its complex regulatory mechanism 1. The protein exhibits both BMP inhibitory and enhancing activities: it directly inhibits BMP signaling by binding to BMP ligands and occupying their type 1 receptor binding sites, while simultaneously enhancing BMP activity through interactions with Chordin, a BMP antagonist 12. TWSG1 plays critical roles in embryonic dorsoventral axis formation and iron homeostasis regulation, where it suppresses hepcidin expression in hepatocytes and contributes to iron dysregulation in thalassemia syndromes 3. In cancer contexts, TWSG1 demonstrates tissue-specific functions, acting as a tumor suppressor in gastric cancer by inhibiting cell proliferation and cycle progression 4, while promoting malignant progression in glioblastoma through Akt pathway activation 56. The protein's expression levels correlate with patient outcomes across multiple cancer types, suggesting potential utility as both a biomarker and therapeutic target 7.