biostudies-literatureShipman KENIDDK NIH HHSNIH HHS619-640https://www.ebi.ac.uk/biostudies/studies/S-EPMC10103310biostudies-literatureUnknown34(4)<h4>Significance statement</h4>Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease causes an unknown impairment in endocytic traffic, leading to tubular proteinuria. The authors integrated data from biochemical and quantitative imaging studies in proximal tubule cells into a mathematical model to determine that loss of ClC-5 impairs endosome acidification and delays early endosome maturation in proximal tubule cells, resulting in reduced megalin recycling, surface expression, and half-life. Studies in a Dent mouse model also revealed subsegment-specific differences in the effects of ClC-5 knockout on proximal tubule subsegments. The approach provides a template to dissect the effects of mutations or perturbations that alter tubular recovery of filtered proteins from the levJournal of the American Society of Nephrology : JASNImpaired Endosome Maturation Mediates Tubular Proteinuria in Dent Disease Cell Culture and Mouse Models.PMC10103310T32 DK007052R01 DK118726F31 DK121394P30 DK079307S10 OD028596S10 OD021627R01 DK125049Edwards AGerges MKashlan OBWeisz OARbaibi YShipman KETan RJBaty CJLong KRCowan IAMarciszyn ALfalseImpaired Endosome Maturation Mediates Tubular Proteinuria in Dent Disease Cell Culture and Mouse Models.<h4>Significance statement</h4>Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease causes an unknown impairment in endocytic traffic, leading to tubular proteinuria. The authors integrated data from biochemical and quantitative imaging studies in proximal tubule cells into a mathematical model to determine that loss of ClC-5 impairs endosome acidification and delays early endosome maturation in proximal tubule cells, resulting in reduced megalin recycling, surface expression, and half-life. Studies in a Dent mouse model also revealed subsegment-specific differences in the effects of ClC-5 knockout on proximal tubule subsegments. The approach provides a template to dissect the effects of mutations or perturbations that alter tubular recovery of filtered proteins from the lev2023-01-01T00:00:00Z2023 Apr2026-07-16T09:27:24.066Z2025-04-05T14:43:59.949ZS-EPMC101033103675812510.1681/ASN.000000000000008410.1681/asn.0000000000000084