The molecular basis underlying the mineralization process associated with the conversion of predentin to dentin is poorly understood. What is clear is that a unique set of non-collagenous proteins (NCPs) participate in the nucleation process and in hydroxyapatite growth during dentin formation. Phosphophoryn (PP), the most abundant NCP in dentin, is secreted by odontoblasts and appears at the mineralization front. Dentin sialoprotein (DSP), another NCP, also appears at the mineralization front, but only accounts for 5-8% of the weight of dentin NCPs. Functionally, PP is believed to be directly involved in tile nucleation process by virtue of its ability to bind to collagen type I, and its high affinity for calcium ions. Based on the analysis of the putative rat PP amino acid sequence, this latter activity is believed due to the highly phosphorylated character of PP, which results from the dual actions of casein kinases I and II at selected domains within PP. The precise role of DSP is currently unknown. In situ studies demonstrate that DSP is substantially expressed in odontoblasts and transiently expressed in preameloblasts. However, no information is currently available to directly explain DSP's role in mineralization. Genetically, we and others have now identified a novel DSP-PP bicistronic mammalian transcriptional unit, suggesting that the functional roles of these two NCPs may also be tightly coupled with respect to dentinogenesis. Certainly, further exciting studies are now needed to explain how this DSP-PP transcriptional unit is finally expressed: whether DSP and PP associate with one another, or with collagen at the mineralization front: and how selective mutations in either gene may influence dentin mineralization.