SLC34familien

SLC34-familien, or the SLC34 family, is a subfamily of the solute carrier (SLC) superfamily that encodes three sodium‑phosphate cotransporters in humans: SLC34A1, SLC34A2 and SLC34A3. These membrane proteins mediate sodium‑dependent uptake of inorganic phosphate (Pi) across apical membranes in epithelial tissues, contributing to phosphate homeostasis in kidney and intestine and in other organs.

SLC34A1, also known as NaPi‑IIa, is primarily expressed in the proximal tubule brush border of the kidney where it reabsorbs filtered phosphate. Defects in SLC34A1 can lead to renal phosphate wasting and disturbances in phosphate balance.

SLC34A2, or NaPi‑IIb, has prominent expression in the small intestine and in alveolar type II cells of the lung. In the intestine, it participates in dietary phosphate absorption; in the lung, it helps clear phosphate from the alveolar space. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis (PAM), a rare recessive lung disease characterized by calcium phosphate microliths within the alveoli.

SLC34A3, known as NaPi‑IIc, is expressed in kidney and intestine and contributes to phosphate reabsorption and absorption. Biallelic mutations in SLC34A3 cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), presenting with rickets and an increased risk of nephrolithiasis.

Regulation of SLC34 transporters involves dietary phosphate intake and hormonal signals such as vitamin D, parathyroid hormone, and the FGF23–Klotho axis, which modulate expression and trafficking in renal tubules. Genetic variants can disrupt phosphate handling, affecting serum phosphate, bone mineralization, and calcification risk.