Similarly, urine PPi excretion corrected for urine creatinine was increased in Npt2a-/- mice (3.0±0.53 micromole/mg, n = 19 vs. WT 1.3±0.42 micromole/mg, n = 9, p = 0.038) (Panel A in S1 Fig). Evaluation of whole kidney gene expression was unchanged for the PPi-generating enzyme Enpp1 (0.004±0.001, n = 9 vs. WT 0.005±0.001, n = 7, p = ns) and decreased for the PPi transporter Ank (0.00015±2.8e-5, n = 9 vs. WT 0.001±0.00014, n = 10, p = 0.007) (Fig 1B and 1C). Expression of the Pi-generating enzyme Entpd5 was decreased (0.06±0.01, n = 9 vs. WT 0.6±0.15, n = 10, p = 0.0073) and expression of Tnsalp, which hydrolyses PPi to Pi, was increased (0.07±0.02, n = 9 vs. WT 0.02±0.004, n = 10, p = 0.0043) (Fig 1D and 1E). Thus, the source of urine PPi in Npt2a-/- mice remains unclear and may be extrarenal, localized to a specific tubular segment inside the kidneys, or regulation may occur on the post-translational level.