THSD4 (thrombospondin type 1 domain containing 4), also known as ADAMTSL6, is a microfibril-associated protein that plays critical roles in extracellular matrix organization and vascular homeostasis. Functionally, THSD4 promotes fibrillin-1 (FBN1) matrix assembly and attenuates TGF-β signaling by facilitating sequestration of latent TGF-β complexes within microfibrils 1. Beyond vascular function, THSD4 promotes hair growth by enhancing dermal papilla-hair matrix interactions through the SDC4-THSD4-CXCL1 signaling axis 2. Clinically, THSD4 is highly relevant to inherited thoracic aortic aneurysm (TAAD). Pathogenic THSD4 variants—including those causing premature termination codons and haploinsufficiency—lead to impaired fibrillin-1 microfibrils and progressive aortic dilation with medial degeneration 1. Genome-wide association studies identified THSD4 among 78 loci associated with ascending aorta size and demonstrate causal associations with aneurysm development 3. Dysregulation of THSD4 expression also occurs in abdominal aortic aneurysm and is associated with extracellular matrix remodeling in vascular smooth muscle cells 4. Beyond aneurysms, THSD4 suppression correlates with gastric cancer chemotherapy resistance via midkine and epithelial-mesenchymal transition pathways 5, and altered THSD4 expression associates with impaired osteogenesis in osteoporosis 6. These findings establish THSD4 as a multifunctional regulator of connective tissue integrity with therapeutic implications for vascular and metabolic diseases.