With increasing evidence highlighting the role of immune dysregulation in orthopedic diseases such as osteoarthritis, osteoporosis, intervertebral disc degeneration, delayed fracture healing, and bone tumors, the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway has emerged as a central mediator of innate immune sensing and sterile inflammation. Here, CGAS is linked to bone neoplasm.