TMEM174 is a proximal tubule-enriched transmembrane protein that functions as a critical regulator of renal phosphate homeostasis 1. Located in the endoplasmic reticulum membrane, TMEM174 directly interacts with the sodium-phosphate cotransporter NPT2A and mediates its degradation in response to phosphate-lowering hormones 1. Specifically, TMEM174 is required for FGF23- and PTH-induced reduction of NPT2A protein levels; TMEM174 knockout mice develop severe hyperphosphatemia with elevated serum FGF23 and PTH, culminating in vascular calcification 1. Beyond phosphate regulation, TMEM174 contains two transmembrane helices that determine its subcellular localization and function 2. Overexpression of TMEM174 enhances AP-1 transcriptional activity and promotes cell proliferation through MAPK signaling pathways, with transcription factor binding sites for CREB and AP-1 identified in its promoter region 23. Clinically, TMEM174 exhibits differential expression across renal cancer types, with elevated expression in papillary renal cell carcinoma and transitional cell carcinoma, suggesting potential involvement in renal malignancy development 4.