/ overexpression impairs neural function.

Pathogenic variants in , a gene encoding for an autophagy adaptor termed ALFY, are linked to neurodevelopmental delay and altered brain size in human probands. While the role of loss-of-function is extensively studied in neurons, little is known about the effects of upregulation in different cell types of the central nervous system (CNS). We show that overexpression of the ortholog, , in either glia or neurons impaired autophagy and locomotion. glial overexpression also increased VNC size and glial nuclei number significantly, whereas neuronal overexpression affected wing and thorax morphology. We identified 79 genes that were differentially expressed and overlapped in flies that overexpress in glial and neuronal cells, respectively. Additionally, upon neuronal overexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondrial function. Our data indicate that glial as well as neuronal upregulation can have detrimental outcomes on neural function.