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Glomerular endothelial cell (GEnC) fenestrations are recognized as an essential component of the glomerular filtration barrier, yet little is known about how they are regulated and their role in disease. We comprehensively characterized GEnC fenestral and functional renal filtration changes including measurement of glomerular and GFR in diabetic mice (BTBR ). We also examined and compared human samples. We evaluated Eps homology domain protein-3 (EHD3) and its association with GEnC fenestrations in diabetes in disease samples and further