Slc34a1, encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), is crucial for maintaining phosphate homeostasis in the kidneys. It is involved in the reabsorption of phosphate from the renal tubules, and its function is significant for normal calcium and phosphate metabolism, which are related to many biological processes and disease states [1,2,3]. Mouse models are valuable genetic tools to study its functions.

In Slc34a1-knockout mice, phosphate depletion and fibroblast growth factor-23 suppression were observed, leading to the development of an idiopathic infantile hypercalcemia (IIH) phenotype. This indicates that defective NaPi-IIa function, caused by Slc34a1 mutations, can induce inappropriate production of 1,25-(OH)2D3, resulting in symptomatic hypercalcemia [1]. In addition, biallelic SLC34A1 variant carriers in humans showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, with a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria [3].

In conclusion, Slc34a1 is essential for maintaining phosphate and calcium balance through its role in renal phosphate reabsorption. The study of Slc34a1 knockout mouse models has significantly contributed to understanding the pathogenesis of idiopathic infantile hypercalcemia, highlighting the importance of this gene in related disease areas [1,3].