Another possible mechanism suggested by our results in Drosophila is a role for oxidative stress, to which RGS14 ortholog mutants are resistant,30 and which has been implicated in mammalian salt sensitivity.54, 55 Establishing the functional role of these genes in salt sensitivity, TGF, GFR, oxidative stress, and CKD will require targeted in vivo studies using knockout and/or transgenic mouse models. Here, RAPGEF5 is linked to chronic kidney disease.