Based on the data in this study, we hypothesize that P311 regulates renal fibrogenesis because (1) P311 levels were significantly increased and P311 seem to be co-localized with TGF-β1- and α-SMA-positive regions in renal fibrosis; (2) interstitial collagen deposition, vimentin and α-SMA expression and macrophage infiltration decreased in P311-deficient mice in a mouse model of UUO-induced fibrosis; and (3) P311 deficiency down-regulated tubular TGF-β1 expression, TGF-β1 receptor expression and TGF-β1/Smad signaling activation. Here, NREP is linked to renal fibrosis.