DIS3 is a catalytic component of the RNA exosome complex with dual 3'-5' exoribonuclease and endonuclease activities 1. In the nucleus, DIS3 processes stable RNAs (rRNA, snRNA, snoRNA), eliminates RNA by-products and aberrant transcripts, and participates in antibody diversification 1. In the cytoplasm, it degrades unstable mRNAs containing AU-rich elements and functions in RNA surveillance pathways 1. Recently, DIS3 was identified as responsible for circular RNA degradation through its endonucleolytic activity independently of the exosome complex, preferentially targeting U-rich circRNA sequences 2. DIS3 mutations occur in approximately 10% of multiple myeloma patients, with deletions of chromosome 13 affecting 40% of cases 3. DIS3 loss-of-function impairs cell cycle progression and centrosome duplication in myeloma cells, leading to genomic instability and potentially contributing to myelomagenesis 4. DIS3 mutations show oncogenic dependencies with specific translocation events and driver mutations in multiple myeloma 5. Despite high mutation frequency, the precise mechanisms linking DIS3 dysfunction to cancer pathogenesis remain incompletely understood 1.