Researchers identified a rare ELASTIN gene variant (p.Gln691X) in a family with bicuspid aortic valve (BAV), the most common congenital heart defect affecting 1-2% of the population. Using zebrafish with both elastin genes knocked out, they demonstrated this variant cannot restore normal heart function, while wild-type ELASTIN can fully rescue cardiac development and valve morphology. The zebrafish model showed reduced stroke volume and malformed aortic valves, mirroring human BAV pathology. This finding expands our understanding of BAV's genetic architecture beyond previously known pathways involving NOTCH1 and GATA genes. While ELASTIN variants are classically associated with Williams-Beuren syndrome and supravalvular aortic stenosis, this work establishes a direct mechanistic link to valve malformation itself. The discovery has immediate clinical relevance for genetic counseling of BAV families and potential therapeutic targeting of extracellular matrix pathways. However, this preprint awaits peer review, and the findings need replication in larger patient cohorts. The zebrafish model, though evolutionally conserved for cardiac development, may not fully capture human valve complexity. This represents solid confirmatory science linking extracellular matrix dysfunction to congenital heart disease.