HAPLN3 (hyaluronan and proteoglycan link protein 3) is a member of the link protein superfamily that functions in hyaluronic acid binding and extracellular matrix organization 1. The protein contains typical modular elements of link proteins and has an estimated molecular mass of 39 kDa 1. HAPLN3 co-localizes with versican around vascular smooth muscle cells and is coordinately upregulated by platelet-derived growth factor, suggesting involvement in pericellular matrix formation 1. In cancer contexts, HAPLN3 demonstrates significant clinical relevance as a potential biomarker and therapeutic target. The gene shows elevated expression in breast cancer tissues compared to normal tissues, with positive correlation to human epidermal receptor 2 staining density 2. In clear cell renal cell carcinoma (ccRCC), HAPLN3 promotes tumor progression by inhibiting apoptosis and promoting epithelial-mesenchymal transition through ERK and Bcl-2 signaling pathways 3. Additionally, HAPLN3 serves as a prognostic biomarker, with hypermethylation detected in circulating tumor DNA of metastatic prostate cancer patients 4. The protein also functions as a modifier gene, with the HAPLN3 p.T34A variant contributing to incomplete penetrance of moyamoya disease 5.