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Research has shown that degenerin/epithelial sodium channels (DEG/ENaCs) are highly involved in both pre- and postsynaptic function, which has led to their hypothesized direct effect on long-term potentiation, addiction, learning, memory, and neural transmission at the neuromuscular junction (NMJ). Dysfunction in homeostatic signaling caused by dysregulation of DEG/ENaCs has been implicated in various neurological and psychiatric diseases to include autism-spectrum disorders (ASD) (Stone et al., 2007), Alzheimer’s disease, Huntington’s disease (Wong et al., 2008), Parkinson’s disease (Arias et al., 2008), epilepsy, and multiple sclerosis (Biagini et al., 2001). Although glial expression of these channels has been documented in various species (Brockway et al., 2002; Feldman et al., 2008; Huang et al., 2010; Yu et al., 2015), there is a marked lack of scientific inquiry into what role these glial DEG/ENaCs play in functional mechanisms (Hill et al., 2017). This proposal seeks to observe the effects of RNAi-induced DEG/ENaC knockdown in glial cells of Drosophila melanogaster through two experiments. In the first experiment, we observed locomotor effects of 15 unique pickpocket (ppk) genes (ppk4, ppk6, ppk7, ppk10, ppk11, ppk13, ppk16, ppk18, ppk19, ppk21, ppk22, ppk26, ppk27, ppk29, ppk31) through RNAi knockdown and subsequent larval roll assay. In the second experiment, we conducted a test for locomotor effects after ppk29 glial-cell rescue of ppk29P¹ mutants at the NMJ using the UAS-gal4 binary expression system (Brand & Perriman, 1993). Statistical data was analyzed and translated into graphs with SPSS. Neither glial ppk knockdown nor ppk29 rescue showed statistically significant results. However, although not the focus of this study, glial ppk knockdown showed limited statistically significant results for sex-specific effects for ppk11 (p = 0.006) and ppk31 (p = 0.004). This data suggests that glial DEG/ENaCs do not play a critical role in synaptic function at the NMJ. Glial DEG/ENaC involvement in other functions remains a possibility.