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Solute carrier family 38 member 6 (SLC38A6) is known to mediate Na\n +<\/jats:sup>\n \u2010dependent net uptake and efflux of small neutral amino acids, but the role it plays in AKI still needs to be explored. In this study, we generated mice with\n Slc38a6<\/jats:italic>\n genetically deleted in tubular epithelial cells by crossing\n Slc38a6<\/jats:italic>\n \n fl\/fl<\/jats:italic>\n <\/jats:sup>\n mice with\n KspCre<\/jats:italic>\n mice, which are transgenic mice that express Cre recombinase exclusively in tubular epithelial cells in the kidney and developing genitourinary tract. The mice were intraperitoneally injected with cisplatin. Separately,\n SLC38A6<\/jats:italic>\n was knocked down in HK\u20102 cells using siRNA, followed by treatment with cisplatin. Blood urea nitrogen (BUN) and Serum Creatinine (SCr) levels were used to measure renal function, and PAS and H&E staining, along with detection of NGAL expression was used to assess kidney injury. Tunel staining and the expression of apoptosis\u2010related proteins were used to detect kidney cell apoptosis. Transcriptome sequencing was performed to explore the mechanism underlying our phenotypic observations, and lipid deposition was determined using Oil Red O staining. The expression of key enzymes of the fatty acid \u03b2\u2010oxidation (FAO) pathway was detected using Western blotting and RT\u2010qPCR. After induction of AKI,\n Slc38a6<\/jats:italic>\n \n fl\/fl<\/jats:italic>\n <\/jats:sup>\n KspCre<\/jats:italic>\n mice exhibited improved renal function, alleviated kidney injury, and decreased tubular cell apoptosis. Similarly, knocking down\n SLC38A6<\/jats:italic>\n in HK\u20102 cells significantly abrogated apoptosis induced by AKI. Transcriptome sequencing data confirmed that several pathways involved in fatty acid metabolism were activated in\n Slc38a6<\/jats:italic>\n \n fl\/fl<\/jats:italic>\n <\/jats:sup>\n KspCre<\/jats:italic>\n mice. Both\n Slc38a6<\/jats:italic>\n \n fl\/fl<\/jats:italic>\n <\/jats:sup>\n KspCre<\/jats:italic>\n mice and\n SLC38A6<\/jats:italic>\n \u2010knocked down HK\u20102 cells exhibited decreased lipid deposition and increased expression of key enzymes of the FAO pathway. We therefore conclude that SLC38A6\u2010deficiency alleviates cisplatin\u2010induced AKI by decreasing cell apoptosis and promoting FAO.\n <\/jats:p>","DOI":"10.1111\/febs.70500","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:02:58Z","timestamp":1774530178000},"page":"5024-5040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\n SLC38A6<\/i>\n <\/scp>\n expression in renal tubular cells accelerates cisplatin\u2010induced acute kidney injury by promoting cell apoptosis"],"prefix":"10.1111","volume":"293","author":[{"given":"Fumeng","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Critical Care Nephrology and Blood Purification, First Affiliated Hospital of Xi'an Jiaotong University Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of 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