The identification of common pathogenic mechanisms in monogenic and endocrine disorders associated with OPLL/DISH, and the development of targeting therapeutics for other relevant pathways such as ACVR1, COL11A2, COL6A, BMP2,4,9, and TGF-β1 are remaining important questions to be addressed. Here, TGFB1 is linked to ossification of the posterior longitudinal ligament of the spine.