SOSTDC1 (sclerostin domain containing 1) is a secreted protein with context-dependent roles in tissue development and disease. In the lung, SOSTDC1 serves as a marker of specialized aerocyte capillary endothelial cells 1, contributing to lung endothelial heterogeneity. SOSTDC1 functions as a BMP antagonist, directly inhibiting BMP2, BMP4, BMP6, and BMP7 signaling in a dose-dependent manner, with potential applications in tooth regeneration—inhibiting SOSTDC1's antagonist USAG-1 promotes tooth development in congenital agenesis models 23. In cancer biology, SOSTDC1 exhibits dual roles: it is downregulated in lung cancer where it acts as a tumor suppressor gene 4, yet is highly expressed in triple-negative breast cancer (TNBC) tumor-initiating cells, where nuclear-translocalized SOSTDC1 promotes homologous recombination DNA repair and Olaparib resistance through CHD1 interactions 5. Metabolically, SOSTDC1 is elevated in type 2 diabetes patients and CD4+ T cell-derived SOSTDC1 promotes lipogenesis while inhibiting lipolysis via LRP5/6-β-catenin signaling, contributing to obesity-induced insulin resistance 6. Additionally, SOSTDC1 expression distinguishes papillary renal cell carcinoma from mucinous tubular and spindle cell carcinoma 7. These diverse functions reflect SOSTDC1's context-dependent regulation of BMP and Wnt signaling across distinct cell types and disease states.