SFSWAP (splicing factor SWAP) is a global negative regulator of pre-mRNA splicing that controls alternative splicing patterns and intron retention across the genome 1. As a splicing factor, SFSWAP modulates the inclusion or exclusion of exons and regulates intron detention, particularly through control of decoy exon usage 1. A key molecular function involves regulating OGT (O-GlcNAc transferase) intron detention, thereby modulating O-GlcNAcylation homeostasis—a reversible post-translational modification affecting thousands of nuclear and cytoplasmic proteins 1. Clinically, SFSWAP dysregulation is associated with several pathological conditions. In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), SFSWAP expression is altered in blood pre-symptomatically and correlates with ataxia severity, making it a candidate biomarker for disease progression 2. Similarly, differential SFSWAP expression distinguishes progressive from non-progressive sarcoidosis in bronchoalveolar lavage cells 3. SFSWAP deficiency impairs inner ear development and function—Sfswap mutant mice exhibit hearing loss, vestibular defects, and reduced hair cell/supporting cell populations, with evidence suggesting genetic interaction with Notch pathway components like Jagged1 4, 5. These findings position SFSWAP as an important regulator of splicing-dependent biological processes with relevance to neurological and immunological disease pathogenesis.