RBM25 is an RNA-binding protein that functions as a key regulator of alternative pre-mRNA splicing with diverse roles in cellular processes and disease. The protein contains a PWI domain that forms a four-helix bundle with an adjacent basic region, creating an enlarged nucleic acid-binding platform 1. RBM25 controls alternative splicing through multiple mechanisms, including binding to G-quadruplex structures in pre-mRNA. Most notably, it regulates BCL-x splicing by binding to an RNA G-quadruplex near the alternative 5' splice site, promoting production of the pro-apoptotic Bcl-xS isoform over the anti-apoptotic Bcl-xL isoform 2. Beyond apoptosis regulation, RBM25 demonstrates broad splicing regulatory functions, controlling alternative splicing of genes like MNK2 in colon cancer, where it promotes oncogenic MNK2b isoform production 3. The protein also regulates ACLY splicing, influencing metabolic rewiring and inflammation in macrophages 4. Clinically, RBM25 shows disease relevance across multiple conditions: it's overexpressed in colon cancer correlating with poor prognosis 3, elevated in preeclampsia where it disrupts trophoblast migration 5, and decreased in rheumatoid arthritis contributing to hyperinflammation 4. The protein's ability to control splicing makes it a promising therapeutic target, with G-quadruplex ligands showing potential to modulate its activity 2.