Fbln2, also known as fibulin-2, is a secreted extracellular matrix (ECM) glycoprotein. It is essential for basement membrane integrity in mammary epithelium and is involved in multiple biological processes such as cell differentiation, proliferation, and apoptosis. It has been associated with signaling pathways like the bone morphogenic protein (BMP) pathway [1]. Fbln2 is of great biological importance as its dysregulation is linked to various diseases. Gene knockout models, such as the fbln2 knockout zebrafish line, have been crucial in studying its functions [1].

In the context of Goldenhar syndrome, a rare craniofacial malformation, fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the BMP signaling pathway [1]. In idiopathic pulmonary fibrosis, knockdown of FBLN2 in human lung fibroblast-derived MRC-5 cells inhibited TGF-β1-induced proliferation, migration, and fibrosis by downregulating vitronectin (VTN) [2]. In multiple sclerosis, genetic FBLN2 deficiency in the experimental autoimmune encephalomyelitis (EAE) model improved behavioral recovery by promoting oligodendrocyte maturation and enhancing remyelination [3]. In gastric cancer, overexpression of FBLN2 reduced cell proliferation and metastasis, while knockdown enhanced these processes, and it was shown to act through the TGFβ/TGIF2 axis [4].

In conclusion, Fbln2 plays essential roles in various biological processes, including craniofacial development, cell-related functions in fibrosis and cancer, and oligodendrocyte maturation. Gene knockout models, especially in zebrafish and mouse models, have significantly contributed to understanding its role in diseases such as Goldenhar syndrome, idiopathic pulmonary fibrosis, multiple sclerosis, and gastric cancer. These findings may help in developing potential screening targets and treatments for related conditions.