RBMS1 is an RNA-binding protein that regulates gene expression at both translational and post-transcriptional levels. Beyond its characterized role as a single-stranded DNA binding protein upstream of MYC, RBMS1 functions as a translational regulator and alternative splicing factor controlling multiple oncogenic and fibrotic pathways. Mechanistically, RBMS1 bridges translation initiation complexes to target mRNAs and modulates alternative splicing through sequence-specific RNA binding. In lung cancer, RBMS1 enhances ferroptosis evasion by promoting SLC7A11 translation, and facilitates metastasis by coordinating S100P translation with YTHDF1 12. In gastric cancer, RBMS1 activates the IL-6/JAK2/STAT3 pathway through MYC-dependent transactivation 3. In triple-negative breast cancer, RBMS1 sustains PD-L1 levels by stabilizing B4GALT1 mRNA, suppressing anti-tumor immunity 4. Clinically, RBMS1 overexpression correlates with poor prognosis across multiple cancers. Beyond oncology, RBMS1 drives cardiac fibrosis by regulating LMO7 alternative splicing to activate TGF-β1 signaling 5, promotes pulmonary fibrosis by stabilizing SUMO2 mRNA 6, and mediates cardiac hypertrophy through CTTN splice-switching 7. Pharmacological RBMS1 inhibition via nortriptyline or antisense oligonucleotides ameliorated fibrotic and hypertrophic phenotypes in mice, establishing RBMS1 as a therapeutic target. A genetic association study identified RBMS1 variants as type 2 diabetes susceptibility loci in the Chinese Han population 8.