The aims of this study were (1) to investigate the functional consequences of C-terminal mutations, including missense and truncating variants located in the PST or NMTS region, (2) to explore the subcellular localization and osteogenic potential of alveolar bone mesenchymal stem cells (aBMSC) derived from a CCD patient with the p.Ser247Valfs*3 mutation, and (3) to review and summarize the existing functional studies on C-terminal mutations in RUNX2. Here, RUNX2 is linked to cleidocranial dysplasia 1.