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Recent advances have identified metabolic reprogramming as a central driver of podocyte injury in diverse glomerular diseases, including diabetic kidney disease and FSGS. Pathologic stimuli, such as hyperglycemia, lipotoxicity, oxidative stress, and inflammatory cytokines, lead to profound alterations in podocyte metabolism, encompassing dysregulation of lipid, glucose, amino acid, and ion handling and activation of immunometabolic pathways. These maladaptive changes result in mitochondrial dysfunction, cytoskeletal disorganization, and inflammatory forms of cell death including pyroptosis and ferroptosis. Mechanistic studies have elucidated the roles of nutrient-sensing pathways (AMP-activated protein kinase, mechanistic target of rapamycin, and sirtuin-1), innate immune sensors (nucleotide-binding oligomerization domain-like receptor family pyrin domain\u2013containing 3 and cyclic GMP-AMP synthase\u2013stimulator of IFN genes), and metabolic enzymes (ceramide synthase 6, glutaminase-2, and ornithine decarboxylase-1) in orchestrating this reprogramming. Emerging evidence supports the therapeutic potential of modulating podocyte metabolism, as exemplified by the renoprotective effects of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, peroxisome proliferator\u2013activated receptor agonists, and targeted inhibitors of inflammasome or lipid pathways. This review synthesizes recent insights into the structural\u2013metabolic coupling in podocytes, dissects the mechanisms of metabolic derangement in disease contexts, and discusses promising therapeutic strategies aimed at restoring metabolic homeostasis. Understanding the intersection between podocyte metabolism and injury response offers novel avenues for the prevention and treatment of chronic glomerular diseases.<\/jats:p>","DOI":"10.1681\/asn.0000000917","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:07:15Z","timestamp":1760375235000},"page":"619-633","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":15,"title":["Podocyte Metabolic Reprogramming and Targeted 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