SRSF5 (serine and arginine rich splicing factor 5) is a nuclear RNA-binding protein that plays a central role in regulating alternative mRNA splicing and constitutive splicing processes 1. Operating primarily within nuclear speckles, SRSF5 modulates the selection of alternative splice sites through its SR protein domain and responds to cellular signaling via phosphorylation and post-translational modifications 2. Under glucose-replete conditions, SRSF5 is acetylated by Tip60 on K125, antagonizing ubiquitin-mediated degradation and promoting the pro-tumorigenic splicing of CCAR1 to enhance glucose metabolism 2. SRSF5 coordinates nuclear speckle-paraspeckle crosstalk during stress through transient RNA binding that facilitates paraspeckle maturation, with helicase-mediated removal essential for maintaining nuclear body identity 3. Dysregulation of SRSF5 is implicated in multiple malignancies: in colorectal cancer, SRSF5-mediated PKM splicing promotes chemoresistance via PKM2-driven glycolysis 4; in pancreatic cancer, CLK1-phosphorylated SRSF5 induces aberrant exon skipping of METTL14 and Cyclin L2, promoting growth and metastasis 5; and in acute promyelocytic leukemia, SRSF5 downregulation induces apoptosis 6. SOX9-regulated SRSF5 expression is critical for maintaining proper insulin secretion in pancreatic beta cells, with loss impairing glucose homeostasis 1.