The role of ILDR2 in podocytes, specialized epithelial cells in the kidney, is still unknown. We investigated the role of ILDR2 in glomeruli and its influence on blood filtration. Ildr2 knockout mice exhibited glomerular hypertrophy and decreased podocyte density, however, did not develop effacement of podocyte foot processes or proteinuria. LC-MS/MS proteomic analysis of isolated glomeruli showed an increase in matrix proteins such as fibronectin and agrin. This suggests a protective role of ILDR2 in glomerulopathies.