Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10–12 nm calcium-binding microfibrils. These microfibrils provide force bearing structural support in elastic and nonelastic connective tissue throughout the body. Mutations altering the protein can result in a variety of phenotypic effects differing widely in their severity, including fetal death, developmental problems, Marfan syndrome or in some cases Weill-Marchesani syndrome.

FBN1 is a 230-kb gene with 65 coding exons that encode a 2,871-amino-acid long proprotein called profibrillin which is proteolytically cleaved near its C-terminus by the enzyme furin convertase to give fibrillin-1, a member of the fibrillin family, and the 140-amino-acid long protein hormone asprosin.

The sequence of fibrillin-1 includes 47 six-cysteine EGF-like domains, 7 eight-cysteine domains homologous with latent TGF-beta binding protein, and a proline-rich region.

The FBN-1 gene is involved in a variety of embryonic developmental programs. The microfibrils that are made from fibrillin-1 contribute to both elastic and non-elastic structures. The formation of the elastic fibers in the heart valves and the aorta require the involvement of both FBN-1 and FBN-2. It has been shown that both FBN-1 and FBN-2, along with the other components of elastic fibers, are expressed in the embryonic semilunar valves as early as 4 weeks of gestation. These molecules interact to form the elastic fibers in the ventricularis layer of the semilunar valves. Fibrillin-1 and fibrillin-2 are also crucial for the development of elastic fibers in the aorta. While expression of fibrillin-2 decreases significantly after fetal development, the expression of fibrillin-1 continues into adulthood. This supports the idea that fibrilin-2 dictates the development of early elastic fibers, while fibrillin-1 provides the structural support of mature elastic fibers.

When mutations in the FBN-1 or FBN-2 genes occur, significant deformations can result from the damage to the extracellular matrix. Marfan syndrome is a congenital disease that arises from a mutation in the FBN-1 gene. This leads to the malformation and subsequent weakening of the microfibrils in the patient’s body, including the structures of the cardiovascular system. The weakened elastic fibers will result in an impaired durability and distensibility in the heart valves and aorta. This provides the explanation for the aortic aneurysms and prolapsed valves that are commonly associated with Marfan syndrome.

Mutations in the FBN1 gene are associated with Marfan syndrome and its variant Marfanoid–progeroid–lipodystrophy syndrome, autosomal dominant Weill–Marchesani syndrome, isolated ectopia lentis, MASS phenotype, and Shprintzen–Goldberg syndrome.

Mutations in FBN1 and FBN2 are associated with adolescent idiopathic scoliosis.

Clinical symptoms of MFS such as aortic root dilation, pulmonary emphysema, atrioventricular valve changes and skeletal muscle myopathy are induced by altered TGF-β activation and signalling. Aortic specific symptoms are closely related to excessive TGF-β signalling in the aortic root wall. TGF-β antagonism via systemic administration of TGF-β neutralising antibody (NAb) averted the development of aortic pathologies associated with MDS, more specifically changes in the aortic wall and progressive aortic dilation. Antagonism of TGF-β also further reduced MFS symptoms where it helped muscle regeneration, architecture and strength, pulmonary alveolar septation and mitral valve morphology.