TBL3 (transducin beta like 3) is a component of the small subunit (SSU) processome, the 70-protein complex responsible for ribosomal small subunit biogenesis. TBL3 belongs to the UTP-B sub-complex and localizes to the dense fibrillar and granular components of the nucleolus, where it functions as a scaffold protein with low mobility in living cells 1. During 18S rRNA processing, TBL3 participates in 5' external transcribed spacer (5'ETS) processing through mechanisms involving the RNA exosome 2. The protein binds U3 snoRNA and coordinates with other SSU processome components to facilitate RNA folding, modification, rearrangement, and cleavage of nascent pre-rRNA. Clinical significance has emerged from studies of repeat expansion diseases. TBL3 aberrantly interacts with expanded CAG repeat transcripts in spinocerebellar ataxia type 2 (SCA2) and Huntington's disease, disrupting rRNA processing in affected brain tissue 3. Additionally, TBL3 is identified as a hub gene linking type 2 diabetes to cancer through ribosome biogenesis pathways 4. These findings suggest that dysregulation of TBL3-mediated ribosomal biogenesis contributes to neurodegeneration and metabolic disease pathogenesis, highlighting TBL3 as a potential therapeutic target in repeat expansion diseases.