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The kidney shows high\n                      <jats:italic>WDR72<\/jats:italic>\n                      expression; its precise localization and function remain unclear. WDR72 is a member of the WD40 repeat domain protein family\u2014a large group of scaffold proteins involved in various pathways, including vesicular trafficking\u2014which has been suggested as a potential role for WDR72. This study investigates WDR72 expression and its role in renal acid\u2013base homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed\n                      <jats:italic>WDR72\/Wdr72<\/jats:italic>\n                      expression in single\u2010cell transcriptome data from human and murine kidneys. We characterized\n                      <jats:italic>Wdr72<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      female and male mice and assessed\n                      <jats:italic>Wdr72<\/jats:italic>\n                      mRNA and protein localization, the ability of the kidney to excrete acid, and the expression and function of the H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptome data showed that\n                      <jats:italic>WDR72\/Wdr72<\/jats:italic>\n                      is highly expressed in intercalated cells and other nephron segments. Immunohistochemistry localized WDR72 mostly at the apical membrane of type A\u2010intercalated cells (A\u2010IC).\n                      <jats:italic>Wdr72<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice exhibited alkaline urine under normal conditions, but only female knockout mice developed a pronounced metabolic acidosis upon dietary acid loading. Western blot analyses revealed sex\u2010dependent WDR72 expression changes with acid loading. Expression of several H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase subunits was dysregulated in\n                      <jats:italic>Wdr72<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      kidneys while their localization in intercalated cells remained intact. Lower expression of H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase subunits was paralleled by reduced H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase activity observed in isolated microperfused collecting ducts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings identify WDR72 as a critical regulator of type A\u2010intercalated cell dependent urinary acidification, modulating H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase activity. The sex\u2010specific metabolic phenotype reveals a novel mechanism underlying sex differences in renal acid handling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70165","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:23:20Z","timestamp":1770200600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>WDR72<\/scp>\n                    Is Required for Urinary Acidification and Normal H\n                    <sup>+<\/sup>\n                    \u2010\n                    <scp>ATPase<\/scp>\n                    Activity in Intercalated Cells in Mice"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-2075","authenticated-orcid":false,"given":"Hannah","family":"Auwerx","sequence":"first","affiliation":[{"name":"Institute of Physiology University of Zurich  Zurich 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