Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is cleaved mainly into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Both DSP and DPP have been implicated to have specific roles in dentin mineralization. We had earlier reported that that DSPP null mice display a phenotype in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Many of the earlier in vitro studies indicated that DPP plays a significant role in initiation and completion of dentin mineralization. We have recently reported our findings on DPP conditional knockout mice that indicate distinct roles of DSP and DPP in dentin mineralization: DSP is involved in regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin. In this review, we summarized lessons learned from mouse models of DSPP, DSP, and DPP.