SOST encodes sclerostin, a secreted glycoprotein that serves as a negative regulator of bone formation through inhibition of the canonical Wnt signaling pathway 1. The protein is expressed predominantly by osteocytes and acts as a molecular brake on bone formation, with its expression regulated by mechanical forces 2. Mechanistically, sclerostin suppresses osteoblast activity by blocking Wnt signaling, which is essential for bone formation and homeostasis 1. Loss-of-function mutations in SOST cause sclerosteosis, characterized by excessive bone formation and skeletal hyperostosis 1. Additionally, a 52-kb deletion removing a SOST regulatory element causes van Buchem disease, which shares similar features of bone overgrowth 3. The clinical significance of SOST has led to therapeutic development, with sclerostin antibodies like romosozumab now approved for osteoporosis treatment 4. Romosozumab works by neutralizing sclerostin, leading to rapid bone formation stimulation and significant fracture risk reduction 4. Plasma sclerostin levels are also emerging as important biomarkers for osteoporosis risk prediction 5. Beyond bone, sclerostin functions as an endocrine factor integrating bone metabolism with systemic energy homeostasis 6.