SLC34A1SLC34A2

SLC34A1 and SLC34A2 are two related human genes that encode members of the SLC34 family of sodium-dependent phosphate transporters. They play essential roles in cellular uptake and systemic phosphate homeostasis, with tissue-specific expression patterns that reflect their distinct physiological functions.

SLC34A1 encodes the transporter known as NaPi-IIa, which is primarily expressed in the brush border of proximal tubule cells in the kidney and also present in the small intestine. SLC34A2 encodes NaPi-IIb, a transporter prominently expressed in the small intestine and airway epithelium, including alveolar type II cells in the lung, with additional expression in other tissues such as the kidney and mammary gland. Both transporters mediate sodium-coupled uptake of inorganic phosphate into cells, contributing to dietary phosphate absorption (SLC34A2) and renal phosphate reabsorption (SLC34A1). Their activity is integrated with hormonal and dietary signals that regulate phosphate balance, including vitamin D and parathyroid hormone.

Clinical significance is most clearly established for SLC34A2, where pathogenic variants cause pulmonary alveolar microlithiasis (PAM), an autosomal recessive lung disorder characterized by calcified microliths in the alveolar spaces and progressive respiratory impairment. Variants in SLC34A1 have been reported in association with disorders of phosphate handling and nephrolithiasis in some studies, but the pathogenic links are less well defined and continue to be investigated. Together, SLC34A1 and SLC34A2 contribute to the coordinated control of phosphate uptake across major physiological barriers.