Calcium and phosphate levels are controlled by active vitamin D, 1,25(OH)₂D₃ (1,25D), which is made in the kidney proximal tubule (PT) cells by the CYP27B1 enzyme and degraded by the CYP24A1 enzyme. PTH activates Cyp27b1 and suppresses Cyp24a1 whereas FGF23 suppresses Cyp27b1 and activates Cyp24a1. 1,25D itself suppresses Cyp27b1 and activates Cyp24a1. In vivo, the balance of serum PTH and FGF23 determines the homeostatic levels of vitamin D hormone. While genomic actions of PTH activation and 1,25D act through the transcription factors (TFs) CREB and VDR, respectively, the mechanisms of PTH suppression of Cyp24a1 and, importantly, genomic control by FGF23 have remained a critical knowledge gap. We previously determined three critical enhancer groups for the control of Cyp24a1 in the PT: promoter proximal (PRO, TSS to ~ -300 bp), Downstream 1 (DS1, +21 kb to +32 kb), and Downstream 2 (DS2, +35 kb to +46 kb). We found that DS2 was more ubiquitous in many tissues and responsible for VDR/1,25D response with PRO whereas, DS1 was only present in PT and was responsible for the bulk of the PTH and FGF23 response, when deleted. We recently mutated the classic pair of VDREs in the PRO region in mice (-150 and -250 bp, C24-V1V2mut mice) and found that while our 1,25D response was abrogated ~90% in non-kidney tissues, the kidney cells maintained ~50% of response due to the presence of DS1 and in fact, VDR binding was maintained in both the DS1 and DS2 regions, albeit reduced. We long hypothesized that the PRO VDREs were perhaps the genomic connection point for the DS1 and DS2 enhancers. However, despite their loss, expression remained, indicating a remaining TF might be uniting these regions. In collaboration with Dr. Ken White’s group at Indiana University School of Medicine, we discovered a PT-specific transcription factor that increases with FGF23 treatment. By ChIP-seq analysis, we found that this TF is tightly associated with VDR across the genome in the kidney and can be co-IPed with VDR demonstrating a physical interaction. This TF bound to both the PRO and DS1 regions and was maintained in the C24-V1V2mut mice. The remarkable feature of this TF was that PTH treatment in mice completely removed it from nearly all genomic enhancers, explaining the sharp Cyp24a1 suppression by PTH. This puts this FGF23-responsive TF at the nexus between both PTH suppression and FGF23 activation in controlling the homeostatic levels of vitamin D metabolism and opens an entirely new area of genomic study in the kidney.