SDE2 is a multifunctional spliceosome-associated protein with dual roles in pre-mRNA splicing and ribosome biogenesis. As a ubiquitin-fold-containing protein, SDE2 functions as both an RNA-binding protein and trans-acting adaptor factor 1. In splicing, SDE2 is activated by ubiquitin-specific proteases that cleave its N-terminal ubiquitin-like domain, generating a short-lived C-terminal fragment that incorporates into spliceosomes 2. This activated form promotes intron-specific splicing, particularly of introns with distant branchpoint-3' splice site spacing, by facilitating spliceosomal association of regulatory factors like Cactin 3. SDE2 also contributes to spliceosome disassembly by docking on catalytic U6 snRNA alongside DHX15 helicase to initiate the transition from active to post-catalytic spliceosomes 4. In ribosome biogenesis, SDE2 binds snoRNAs (SNORD3 and SNORD118) to enable cleavage of 47S rRNA precursors 1. Additionally, SDE2 participates in genome surveillance by regulating replication stress responses through PCNA-dependent processing and subsequent degradation via the Arg/N-end rule pathway 56. SDE2 depletion causes widespread splicing defects, ribosome biogenesis impairment, and cell death 1, establishing it as essential for fundamental cellular processes.