Sfswap, a poorly characterized splicing factor, serves as a global regulator of retained intron splicing and exon skipping, primarily acting as a negative regulator of pre-mRNA splicing and a positive regulator of intron retention. It is involved in the regulation of O-GlcNAcylation, a key post-translational modification, by being a trans-acting factor regulating OGT intron detention. The O-GlcNAcylation pathway, mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), forms a feedback loop to maintain O-GlcNAc homeostasis [1,3].

In mouse models, an insertional mutation in the Sfswap gene leads to vestibular and cochlear defects consistent with disrupted Notch signaling. Homozygous Sfswap mutants display hyperactivity, circling behavior, and significantly impaired hearing. The cochlea of newborn mutants shows a reduction in outer hair cells and supporting cells, along with ectopic inner hair cells. Genetic interaction between Sfswap and Jag1 is indicated as Jag1;Sfswap compound mutants have more severe inner ear defects than single mutants [2].

In summary, Sfswap plays crucial roles in pre-mRNA splicing regulation, especially in the context of O-GlcNAcylation. The study of Sfswap in mouse models has revealed its significance in inner ear development and Notch signaling-related processes, providing insights into the mechanisms underlying inner ear-associated diseases.