Some macromolecules, such as osteopontin (OPN) [6], matrix Gla protein (MGP) [7], bikunin [8], and Tamm-Horsfall proteins [9], have been identified in both the urine and kidney stone matrix, and their gene variants have also been reported to affect the risk of kidney stone disease [10–12]. Here, SPP1 is linked to nephrolithiasis.