ADAMTS3 is a secreted zinc metalloendopeptidase that primarily functions in collagen biosynthesis and extracellular matrix organization 1. Its primary enzymatic role is cleaving propeptides of type II collagen prior to fibril assembly, a process essential for proper collagen maturation 2. Beyond collagen processing, ADAMTS3 regulates developmental angiogenesis and lymphangiogenesis through VEGF-C pathway dysregulation 3. Mechanistically, ADAMTS3 operates as part of the procollagen N-proteinase subfamily, with its transcriptional activity regulated by SP1 transcription factors 2. The protein contains structural segments connected by loops, where mutations can destabilize critical domains and disrupt secondary structures 4. Clinically, loss-of-function ADAMTS3 mutations cause Hennekam Lymphangiectasia-Lymphedema Syndrome 3, characterized by lymphatic dysplasia, intestinal lymphangiectasia, and severe lymphedema 4. In acquired diseases, ADAMTS3 is implicated in glioblastoma tumorigenicity, where elevated expression in glioma stem cells promotes proliferation and self-renewal; knockdown suppresses stemness and tumor formation 5. ADAMTS3 upregulation also associates with cancer-associated cachexia in lung cancer and may influence bronchodilator response in asthma 67. These findings suggest ADAMTS3 as a potential therapeutic target in multiple malignancies and developmental disorders.