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In this study, we systematically identified 14 SWEET homologs in the genome of sacred lotus (Nelumbo nucifera) and validated their transport activity for both hexoses and sucrose. Subsequent analysis revealed that stress-responsive elements are the most enriched promoter sequences of NnSWEET genes. Quantitative expression profiling of the members found that NnSWEET4a was strongly upregulated under salt stress. NnSWEET4a was localized at the plasma membrane; its expression conferred salt sensitivity in both yeast and Arabidopsis thaliana. Transgenic Arabidopsis lines overexpressing NnSWEET4a exhibited substantial downregulation of the SOS3\u2013SOS2\u2013SOS1 signaling module and concomitant alterations in cellular sugar homeostasis. Further analysis revealed that exogenous sugar application aggravated salt sensitivity and SOS pathway inhibition in NnSWEET4a transgenic plants, and NnSWEET15-overexpressing Arabidopsis recapitulated identical phenotypic and molecular responses, including salt sensitivity and repression of SOS genes. These findings indicate that NnSWEET4a impairs salt tolerance through disruption of sugar homeostasis. The results establish a mechanistic framework for future investigations into SWEET-dependent regulation of sugar homeostasis and salt stress adaptation.<\/jats:p>","DOI":"10.3390\/plants15162542","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:51:05Z","timestamp":1787327465000},"page":"2542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Overexpression of Lotus NnSWEET4a Alters Sugar Homeostasis and Induces Salt Hypersensitivity in Arabidopsis"],"prefix":"10.3390","volume":"15","author":[{"given":"Shilong","family":"Zhao","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Lu","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyue","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-4209","authenticated-orcid":false,"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6534-0485","authenticated-orcid":false,"given":"Jiashi","family":"Peng","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"},{"name":"Hunan Provincial Engineering Research Center for the Deep Processing and Health Benefits of Xianglian, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-357X","authenticated-orcid":false,"given":"Tianyu","family":"Gu","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.plantsci.2014.04.013","article-title":"Lessons from crop plants struggling with salinity","volume":"226","author":"Cabot","year":"2014","journal-title":"Plant Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6663","DOI":"10.1038\/s41467-021-26907-3","article-title":"Global predictions of primary soil salinization under changing climate in the 21st century","volume":"12","author":"Hassani","year":"2021","journal-title":"Nat. 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