Calcium and phosphorus are irreplaceable components of life. Tracking the fate of calcium and phosphorus in organisms deserves high attention due to their relevance in bone metabolism and subsequently animal health. Indeed, bone serves as reservoir for calcium and phosphorus, whose formation and resorption follow specific molecular routes including hormones, receptors, and transcription factors. The objective of the study was to analyze the genetic variation of major components driving mineral utilization such as calcitonin receptor, calcium sensing receptor, fibroblast growth factor 23 (FGF23), parathyroid hormone receptor, osteopontin, stanniocalcin 1, RAF-type zinc finger domain containing 1 (TRAFD1), and vitamin D receptor. A German Landrace pig population (n = 360) was used to perform an association analysis between selected single nucleotide polymorphisms (SNP) and relevant serum parameters (calcium, phosphorus, calcium/phosphorus ratio, alkaline phosphatase). Analyzed SNPs in FGF23 (rs710498025) and TRAFD1 (rs345195312) were significantly (p ≤ 0.05) associated with the serum calcium/phosphorus ratio and serum phosphorus levels, respectively. This might represent a modulation of the homeostatic balance between calcium and phosphorus. Furthermore, TRAFD1 is known to be involved in skeletal disorders which emphasize its link to phosphorus utilization and immune system. However, none of the analyzed genetic variants of these major regulators of phosphate and calcium homeostasis showed significant associations after correction for multiple testing (q value > 0.05). Thus, minor contributors as well as unknown and yet to be elucidated regulators of mineral homeostasis need to be characterized towards the implementation of improved phosphorus efficiency in pig breeding programs.