Kidney stones afflict about 1 in 11 Americans and the most common stones are composed of calcium oxalate (CaOx), but no therapies exist to treat CaOx kidney stone formation at its earliest stages. Recent evidence strongly suggests that patients who retain stones in their kidneys during the earliest phase of stone growth solely via the mechanism of Randall’s (interstitial) plaque (RP) have a fundamentally different pathology of early stone growth than do those patients who retain stones in the kidney via other mechanisms. In spite of how common this pathway seems to be, the mechanism by which early stone growth proceeds on RP—and how this form of early stone growth may be different from other mechanisms—is not understood well enough to direct therapies toward blocking the growth of early stones in this most-common of CaOx patients. The overall objective for the present proposal is to map the mineral and protein transitions as CaOx stones initiate on Randall’s plaque. The work proposed here is foundational for learning how to block the genesis of these stones, and thus to provide treatment to prevent stones from forming on Randall’s plaques.