In summary, we found that lower levels of BMPs caused the deficiency of BMP/Smad signaling in IDD patients, leading to the impairment of the pSmad1/5/8-HDAC1-Smad4 complex and resulting in the induction of PUMA. The accumulation of the PUMA-encoding protein PUMA initiated apoptosis and resulted in the occurrence of IDD. Here, SMAD4 is linked to intervertebral disk degenerative disorder.