Pontocerebellar Hypoplasia (PCH) is a rare congenital disorder displaying autosomal recessive inheritance characterized by hypoplasia and atrophy of the cerebellar cortex, dentate nuclei, pontine nuclei and inferior olives. Two of the RNA exosome subunits, EXOSC3 and EXOSC8, have been identified as mutated in PCH type 1 patients, who also exhibit a spinal muscular atrophy phenotype indicating possible motor neuron involvement too. Drosophila has a predicted single copy of all of the known RNA Exosome subunits, and is therefore an excellent model organism to investigate potential molecular mechanisms. We have obtained and are generating mutants using imprecise excision and CRISPR in as many of the RNA exosome subunits as possible with the purpose of comparing their null phenotypes. We have already discovered in rrp4 mutants that the expression of key neurodegenerative disease-related proteins is altered, and are further investigating this. Using this data, we are targeting specific pathways to determine whether their RNAi phenotypes can be suppressed using genetic interactions and determining whether the molecular mechanisms are similar to those we are in parallel studying in the PCH-associated TSEN complex. We are in parallel determining whether the cellular and molecular phenotypes we observe are also seen in human cell lines. We hope that our data will give clues to potential treatments, which are presently only supportive in nature.