SMAD9 is a receptor-regulated SMAD protein that functions as a BMP-responsive transcriptional modulator involved in multiple physiological and pathological processes. As a key component of BMP signaling, SMAD9 translocates to the nucleus upon activation by BMP type 1 receptor kinase, where it acts as a DNA-binding transcription factor regulating gene expression through RNA polymerase II 1. SMAD9 plays critical roles in osteoblast differentiation and stem cell differentiation; recent evidence shows that lncRNA KCNMA1-AS1 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by directly activating SMAD9 signaling 2. Beyond bone biology, SMAD9 exhibits oncogenic properties in neuroblastoma, forming a positive transcriptional feedback loop with MYCN that sustains high-risk disease 3. Clinically, SMAD9 variants have definitive evidence for causing pulmonary arterial hypertension (PAH), with pathogenic mutations identified in PAH patients; however, sotatercept treatment shows consistent efficacy regardless of SMAD9 variant status 14. Additionally, SMAD9 expression is elevated in chr13 thromboembolic pulmonary hypertension 5, and genetic polymorphisms in SMAD9 associate with essential hypertension risk in Han Chinese populations 6. Emerging evidence suggests a human SMAD9 (GCC)-repeat may influence late-onset Alzheimer's disease and vascular dementia susceptibility 7.