Sarfraz Ahmed, Sana Iram, Amar Akash, Kwonyoung Kim, Jihoe Kim
Tetranectin (TN), also known as C-type lectin domain family 3 member B (CLEC3B), is a secreted glycoprotein originally identified through its high-affinity interaction with plasminogen. Although initially linked to fibrinolysis, TN is now increasingly recognized as an extracellular regulator associated with matrix remodeling, bone development, tissue repair, and disease-related proteolytic processes. Dysregulated TN expression has been reported in a broad range of pathological conditions, including cancer, cardiovascular disease, inflammatory disorders, and neurodegenerative states. In this review, we summarize current knowledge of TN with emphasis on its molecular architecture, ligand-binding properties, trimeric organization, and regulatory mechanisms. We further discuss its context-dependent biological functions, with particular attention to how tissue-specific and compartment-specific TN patterns may influence disease progression and clinical interpretation, especially in oncology. In addition, we evaluate the evidence supporting TN as a diagnostic and prognostic biomarker and consider its emerging therapeutic relevance. Finally, we outline the major challenges that currently limit clinical translation and highlight key directions for future investigation.