LTBP3 (latent transforming growth factor beta binding protein 3) is a critical extracellular matrix protein that regulates transforming growth factor beta (TGF-β) activation and skeletal development. LTBP3 functions primarily by maintaining TGF-β in a latent state through covalent disulfide bonding with the latency-associated peptide (LAP), forming the large latent complex (LLC) that sequesters TGF-β in the extracellular matrix 1. This complex prevents premature TGF-β activation while enabling integrin-dependent release when needed 1. LTBP3 plays essential roles in bone morphogenesis, tooth development, and skeletal remodeling through TGF-β regulation 2. Pathogenic LTBP3 variants cause Dental Anomalies and Short Stature syndrome (DASS), characterized by amelogenesis imperfecta, hypodontia, short stature, and brachyolmia 3. Beyond skeletal manifestations, LTBP3 mutations associate with serious cardiovascular complications including thoracic aortic aneurysm, aortic dissection, aortic root dilatation, and mitral valve prolapse 45. Recent evidence reveals LTBP3 involvement in keloid pathogenesis, where lactate stimulates LTBP3 transcription and TGF-β1 secretion, promoting fibroblast collagen overproduction 6. Both homozygous and heterozygous LTBP3 mutations demonstrate phenotypic expression, expanding the disease spectrum 3.