PURPOSE OF STUDY: Angelman Syndrome (AS) is a neurodevelopmental disorder caused by deficiency in UBE3A, a ubiquitin E3 ligase, which targets proteins for degradation. Although the genetic cause for AS has been known for decades, how UBE3A deficiency leads to brain dysfunction remains largely unknown. Our previous research has shown that over-activation of mTORC1 contributes to AS pathogenesis in an AS mouse model. mTOR is an evolutionally conserved protein kinase whose full activation requires lysosomal recruiting through interaction with p18. We therefore investigated changes in localization and levels of p18 in brains of both wild-type (WT) and AS mice as a function of age. METHODS USED: Brains of male WT and AS mice were harvested at ages 1, 2–4, and 6–8 months, and sliced into 20 micrometre coronal sections. Brain sections were processed for immunohistochemistry with antibodies against p18 and LAMP2, a lysosomal membrane protein. Images of different brain regions, including the hippocampal CA1 region, were acquired with a confocal microscope. P18 expression and co-localization with LAMP2 in both soma and dendrites were quantified with ZEN software and analysed with Prism software. SUMMARY OF RESULTS: Our preliminary results showed that levels of lysosome-localised p18 in the soma of hippocampal CA1 neurons were significantly higher in AS mice from all age groups, as compared to WT mice. Although levels of lysosome-localised p18 in apical dendrites of hippocampal CA1 neurons were also significantly increased in AS mice, as compared to WT mice in the 2–4 month groups, differences in other age groups were not significant. CONCLUSIONS: These preliminary results confirmed our unpublished Western Blot results that p18 levels in hippocampus of young adult AS mice were increased, as compared to WT mice. These results also indicated that the increased p18 expression is mostly localised on lysosomes. They also suggest that changes in p18 expression could participate in the postnatal development of pathology in AS, as well as its persistence in adulthood. Whether increased p18 levels contribute to mTOR lysosomal recruiting and activation in AS mice is currently under investigation.