The expression and roles of syndecan-4 in the kidney were investigated. Syndecan-4 expression was detected in the ureteric bud invaginating into the metanephric mesenchyme at 11.5 gestational days, and remained in the collecting ducts, distal renal tubules, glomeruli, and some capillaries between renal tubules until the mature kidney stage. However, organogenesis of the kidney was normal in syndecan-4–deficient (Synd4 [−/−]) mice. Although most renal functions of Synd4 (−/−) mice were not impaired, a significant increase in susceptibility to κ-carrageenan–induced renal damage was observed in these mice. κ-Carrageenan was heavily deposited in the collecting ducts of Synd4 (−/−) mice and caused obstructive nephropathy, leading to death of 7 of 24 Synd4 (−/−) mice within 7 days after administration, whereas none of 24 Synd4 (+/+) mice died. After administration of κ-carrageenan, blood urea nitrogen of Synd4 (−/−) mice was significantly higher than that of Synd4 (+/+) mice. Thus, syndecan-4 may function to prevent κ-carrageenan deposition in the collecting ducts.