In summary, our study uncovered that loss of FLNB negatively impacts TGFβ and BMP signaling through its role in modulating inhibitory Smads and provides a Mendelian disease mouse model to study disc degeneration and progressive fusions, a common disease of aging, and suggests a more nuanced treatment strategy for disc degeneration. Here, TGFB1 is linked to intervertebral disk degenerative disorder.