EXOSC4 is a non-catalytic structural component of the RNA exosome complex, a multi-subunit ribonuclease machinery essential for cellular RNA processing and degradation 1. In the nucleus, EXOSC4 participates in maturation of stable RNAs including rRNA and snRNA, and eliminates defective mRNAs and non-coding transcripts 1. In the cytoplasm, it contributes to mRNA turnover and degradation of inherently unstable transcripts containing AU-rich elements 1. EXOSC4 binds RNA substrates and serves as a scaffold for catalytic subunit association within the exosome core complex 1. Pathogenic biallelic variants in EXOSC4 cause severe neurodevelopmental disorders characterized by global developmental delay, growth restriction, intracerebral calcifications, and kidney failure 1. At the molecular level, disease-associated variants reduce EXOSC4 protein stability and exosome assembly, leading to accumulation of unprocessed ribosomal RNA precursors and impaired translation 1. Clinically, EXOSC4 dysregulation associates with multiple malignancies. EXOSC4 amplification occurs across cancer types and represents a therapeutic target in pan-cancer ribosome biogenesis programs 2. High EXOSC4 expression independently predicts poor prognosis in diffuse large B-cell lymphoma and is required for pancreatic cancer cell survival 34. In colorectal and breast cancers, EXOSC4 overexpression promotes proliferation, invasion, and stem cell traits through multiple signaling pathways 56.