CLEC3B (tetranectin) is a calcium-binding C-type lectin that functions as a plasminogen and kringle-4 binding protein 1. Primary functions include involvement in extracellular matrix organization, bone mineralization, and retinal homeostasis 1. Mechanistically, CLEC3B exerts tumor-suppressive effects across multiple cancer types. In hepatocellular carcinoma (HCC), downregulated CLEC3B in exosomes promotes metastasis and angiogenesis through AMPK and VEGF signaling suppression 2. In cholangiocarcinoma, CLEC3B overexpression inhibits proliferation, migration, and invasion via Wnt/β-catenin pathway inhibition; calcium enhances these effects 3. Reduced CLEC3B expression serves as an independent prognostic marker in HCC, predicting poor survival outcomes 45. Disease relevance is substantial. Pathogenic CLEC3B variants cause autosomal dominant macular-retinal dystrophy, characterized by subretinal deposits, reduced retinal thickness, and impaired visual function 1. In osteoarthritis, CLEC3B upregulation following estrogen receptor-α loss promotes chondrocyte hypertrophy and inflammation, accelerating cartilage degradation 6. Clinically, CLEC3B represents a promising prognostic biomarker and potential therapeutic target across multiple malignancies and degenerative diseases, with calcium signaling modulation offering additional therapeutic leverage.