Proper development, function and maintenance of the central nervous system (CNS) are reliant on the intricate relationship between glia and neurons. Glia cells possess a variety of key functions such as maintaining homeostasis, providing neurons with trophic support and the uptake and recycling of neuronal debris. Disruptions in glial function have been implicated in neurological disorders. Despite their obvious importance in the CNS, glia cells remain much less characterized than their neuronal counterparts. With its wide array of genetic tools and its low glia-to-neuron ratio, Drosophila melanogaster presents itself as a useful model organism in studies of glial characterization. Rap/Fzr, an activator of the Anaphase Promoting Complex/Cyclosome (APC/C), a E3 ubiquitin ligase, is the Drosophila homolog of the mammalian Cdh1. Previous studies have shown that proper function of the APC/C regulates glial differentiation in the CNS (Kaplow et al., 2008). Our studies show that targeted pan-glial expression of Rap/Fzr/Cdh1 results in the reduction of glia number in the CNS of 3rd instar larvae. Adult Drosophila with reduced number of glia cells exhibit progressive age-dependent phenotypes such as temperature-sensitive paralysis and vacuolization of the brain, as well as significant lifespan reduction. Employing glia subtype specific GAL4 drivers, we have identified astrocyte-like glia as a critical cell type in neuroprotection. Targeted expression of Rap/Fzr to astrocyte-like glia results in temperature-sensitive paralysis and lifespan reduction. These neurodegenerative phenotypes suggest a vital role for astrocyte-like glia in neuroprotection.