EXOSC3 encodes a non-catalytic structural component of the RNA exosome complex, a highly conserved ribonuclease machinery essential for RNA processing and degradation 1. As part of the catalytically inactive exosomal core complex, EXOSC3 stabilizes the hexameric ring of RNase PH-domain subunits and facilitates RNA binding and presentation for ribonucleolysis 2. In the nucleus, the exosome processes stable RNAs (rRNA, snRNA, snoRNA) and eliminates defective transcripts, while cytoplasmic exosome activity degrades unstable mRNAs and enforces RNA surveillance 1. Recent evidence indicates EXOSC3 interacts with the RNA helicase DDX1 in neuronal cells, modulating R-loop accumulation and gene expression regulation 3. Recessive EXOSC3 mutations cause pontocerebellar hypoplasia type 1b (PCH1b), a severe neurodegenerative disease characterized by cerebellar atrophy, progressive microcephaly, spinal motor neuron degeneration, and profound developmental delay 21. PCH1b presents as various neuromuscular phenotypes including motor neuronopathy and non-5q spinal muscular atrophy 4. Disease-causing mutations reduce EXOSC3 affinity for G-rich RNA sequences, impairing RNA-binding capacity 5. Notably, EXOSC3 mutations also cause eculizumab-nonresponsive atypical hemolytic uremic syndrome, suggesting pleiotropic effects of defective RNA exosome function 6. The tissue-specific neurological manifestation remains incompletely understood.