EXOSC5 encodes a non-catalytic structural component of the RNA exosome complex, a critical ribonuclease machinery involved in RNA processing and degradation 1. The protein functions as part of the nine-subunit exosome core complex (Exo-9) that processes and degrades various RNA species, including rRNA, mRNA, and non-coding RNAs in both nuclear and cytoplasmic compartments 1. EXOSC5 contributes to the structural integrity of the complex and facilitates RNA binding and presentation for ribonucleolysis 1. Disease-causing biallelic variants in EXOSC5 lead to a neurodevelopmental disorder characterized by developmental delays, short stature, cerebellar hypoplasia, hypotonia, and feeding difficulties 1. A distinctive clinical feature is the occurrence of cardiac conduction abnormalities, including complete heart block and ventricular tachycardia, which pose risks for sudden cardiac death 2. Functional studies demonstrate that pathogenic EXOSC5 variants cause defects in RNA exosome function and alter protein-protein interactions within the complex 13. Additionally, EXOSC5 has emerged as a potential biomarker in cancer contexts, with upregulated expression associated with poor prognosis in lung adenocarcinoma and endometrial carcinoma, where it promotes tumor progression and cancer stem cell maintenance 45.