WNT1 is a secreted signaling protein that serves as a ligand for frizzled family receptors and functions primarily in the canonical Wnt/β-catenin signaling pathway 1. The protein plays essential roles in bone development and homeostasis, with loss-of-function mutations causing osteogenesis imperfecta type XV, characterized by severe skeletal dysplasia, low bone mass, and frequent fractures 2. WNT1 variants significantly impair protein secretion and activity, leading to porous bone structure and enhanced osteoclastic activities 2. Single-cell transcriptomic analysis reveals that WNT1 loss disrupts normal differentiation trajectories of skeletal progenitors, resulting in impaired osteocyte maturation, excessive CXCL12+ progenitors, and abnormal cell populations with adipogenic characteristics 2. Beyond bone biology, WNT1 is implicated in cancer development, with elevated expression observed in polycystic ovarian syndrome oocytes 3 and its signaling contributing to tumor progression in mammary cancer models 14. In osteosarcoma, WNT1 hyperexpression is regulated by Sox9 and correlates with advanced clinical staging 5. The protein also functions as a bone-derived signaling factor involved in bone-muscle crosstalk 6.