SRSF12 is a serine/arginine-rich splicing factor that functions as a negative regulator of pre-mRNA splicing. Unlike most SR proteins that promote exon inclusion, SRSF12 antagonizes splice site recognition and promotes exon skipping 1. Mechanistically, SRSF12 localizes to nuclear speckles and interacts with core splicing components and regulatory factors 2. SRSF12 is notably primate-specific in expression, showing high levels in human testis, oocytes, and brain tissue, where it orchestrates tissue-specific gene expression programs including meiosis and testis-specific genes 2. Functionally, SRSF12 regulates alternative splicing of specific transcripts; for instance, it generates particular LAMA3 splice isoforms that suppress neurite outgrowth 3. In disease contexts, SRSF12 dysfunction has clinical significance: its downregulation in pancreatic cancer correlates with poor prognosis and enhanced tumor innervation, indicating it acts as a tumor suppressor 3. Additionally, SRSF12 is upregulated during pro-inflammatory macrophage polarization and is essential for proper immune gene expression 4. SRSF12 overexpression paradoxically induces cell death and mitotic arrest through both its RNA-recognition motif and intrinsically disordered C-terminal domain 2, suggesting cellular-context-dependent effects.