Background: Although glycosaminoglycan-induced GAPDH prefibrillar species accelerates ␣-synuclein aggregation, its role in toxicity remains unclear. Results: The toxic effect exerted by ␣-synuclein oligomers on cell culture was abolished by GAPDH protofibril, which was identified and structurally characterized. Conclusion: GAPDH protofibrils can efficiently sequester ␣-synuclein toxic oligomers. Significance: GAPDH protofibrils may play an important role in neuronal proteostasis and could open a novel therapeutic strategy for synucleinopathies.