SLC12A1 and hyperuricemia: Beyond these, we observed additional phenotypic alterations that were not observed before, including (i) the progressive changes of TAL cells from unfolded protein response in young mice to marked apoptosis in old mice (Figs 2 and 3), (ii) the major defects in the apical translocation of key TAL transporters NKCC2 and ROMK (Fig 7), (iii) the severe oliguria resembling ESRD in old mice (Table 1; Fig 6), and (iv) the hyperuricemia in both young and old mice and the overexpression of both NHE3 and URAT1 in the proximal tubules (Fig 8).