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During AKI, autophagy is typically activated to eliminate protein aggregates and damaged organelles; however, sustained autophagy can contribute to maladaptive repair and fibrosis. Using a GSD\u2010Ia mouse model, we demonstrate that renal G6Pase\u2010\u03b1 deficiency results in heightened autophagy activation, as indicated by increased expression of multiple autophagy\u2010related components and enhanced autophagic flux. Notably, both positive regulators of autophagy, including sirtuin\u20101, forkhead box O3a, and AMP\u2010activated protein kinase, as well as the key negative regulator, mammalian target of rapamycin (mTOR), were concurrently activated in the kidneys of GSD\u2010Ia mice. Previous studies have shown that in response to AKI, renal levels of cyclin G1 (CG1) and cyclin\u2010dependent kinase 5 (CDK5) increase, promoting maladaptive dedifferentiation, G2\/M cell cycle arrest in proximal tubular epithelial cells, and the formation of a TOR\u2010autophagy spatial coupling compartment. This sequence of events contributes to profibrotic factor production and accelerates the progression of kidney disease. In this study, we observed a significant elevation of renal CG1 and CDK5 in GSD\u2010Ia mice with enhanced autophagy, suggesting a potential mechanistic link to the development of renal fibrosis in GSD\u2010Ia. A deeper understanding of these pathways may facilitate the development of targeted therapies for GSD\u2010Ia nephropathy.<\/jats:p>","DOI":"10.1002\/jimd.70127","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T05:52:42Z","timestamp":1765259562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Persistent Activation of Renal Autophagy Contributes to Nephropathy in Murine Glycogen Storage Disease Type Ia"],"prefix":"10.1002","volume":"49","author":[{"given":"Cheol","family":"Lee","sequence":"first","affiliation":[{"name":"Section on Cellular Differentiation, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Pratap","sequence":"additional","affiliation":[{"name":"Section on 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