WNT16 is a secreted Wnt ligand that functions as a positive regulator of bone homeostasis and a protective regulator against osteoarthritis progression 1. As a member of the Wnt family, WNT16 signals through frizzled receptors to activate both canonical and non-canonical Wnt signaling pathways 2. In bone metabolism, osteoblasts secrete WNT16 to suppress osteoclast differentiation and promote bone formation 3. Osteocyte-specific WNT16 overexpression significantly increases cortical and trabecular bone mass, bone strength, and expression of osteoblast markers including alkaline phosphatase and osteocalcin 4. Genome-wide association studies identified WNT16 as the strongest genetic determinant of forearm fracture risk, with bone-site-specific effects 5. Beyond skeletal biology, WNT16 expression is dysregulated in cancer contexts: it is upregulated in gastric adenocarcinoma 6 and downregulated in nodular basal cell carcinoma 7. In osteoblast differentiation on biomimetic implants, WNT16 promotes cell proliferation while inhibiting differentiation through microRNA-145-mediated feedback mechanisms 2. These findings establish WNT16 as a promising therapeutic target for skeletal diseases including osteoporosis and osteoarthritis.