Updated project metadata. Lead (Pb2+) is a heavy metal ubiquitously present in the environment, with unknown essential functions to sustain life. The detrimental effects of Pb2+ on health are known since ancient times, which is also well supported by scientific literature. Incidentally, Pb2+ toxicity is more severe in children than in adults. Various studies highlight the drastic effects of Pb2+ exposure on memory and cognition. However, the exact signalling pathways affected by Pb2+ are still unclear. In the present study, we exposed rat pups to Pb2+ acetate through maternal lactation from day P0 till weaning. The impact of early Pb2+ exposure to spatial cognition was tested using partially baited radial arm maze task three months after weaning. Furthermore, to study the effect of Pb2+ exposure on SUMOylation, the synaptosomal fractions from the hippocampus were purified, and mass spectrometry-based proteomic analysis was performed. Results from behavioral tests revealed that Pb2+ exposure early in life caused severe impairments in spatial cognition with increased reference memory errors and a reduced number of correct choices in PBRAM test. The proteomic analysis revealed differentially altered proteins in Pb2+ exposed rats compared to controls, including SUMO target proteins. Thus, our findings suggest that SUMOylation is a vital protein modification that plays an essential role in memory consolidation.