FBN2 (fibrillin 2) encodes a cysteine-rich glycoprotein that serves as a primary constituent of extracellular microfibrils 1. As a major structural component of the extracellular matrix, FBN2 is essential for tissue biomechanical properties and is hypothesized to guide elastogenesis, particularly in elastic fiber formation 1. FBN2 regulates elastin deposition by interacting directly with lysyl oxidase, and its expression is critical for elastic network synthesis in skin 2. The protein polymerizes extracellularly as parallel bundles of head-to-tail monomers, with calcium binding rigidifying monomeric and supramolecular structures 1. Mutations in FBN2 cause congenital contractular arachnodactyly (CCA), an autosomal dominant connective tissue disorder 1. Compound heterozygous mutations in both COL1A2 and FBN2 produce more severe skeletal abnormalities than single-gene mutations, suggesting synergistic effects on bone development 3. FBN2 genetic variants are associated with sports-related musculoskeletal injuries, including Achilles tendinopathy and anterior cruciate ligament ruptures 4. Genome-wide association studies identified FBN2 as a novel locus associated with Alzheimer's disease risk 5. De novo FBN2 variants have been identified in neurodevelopmental disorders with intellectual disability 6. These findings establish FBN2 as a critical extracellular matrix component with pleiotropic effects on skeletal, connective, and neurological health.