RBMS3 is an RNA-binding protein that recognizes poly(A) and poly(U) oligoribonucleotides and regulates mRNA stability and expression through interactions with 3′-untranslated regions. The protein functions in negative regulation of Wnt/β-catenin signaling and also participates in non-RNA-binding protein–protein interactions that regulate ubiquitin-mediated protein degradation 1. In cancer contexts, RBMS3 loss or downregulation promotes disease progression. In glioblastoma, RBMS3 induces a circular RNA encoding a functional peptide that suppresses vasculogenic mimicry and inhibits tumor cell proliferation and invasion 2. In hepatocellular carcinoma, RBMS3 loss drives sorafenib resistance by impairing TRIM21-mediated ubiquitination of the pro-angiogenic factor ANGPT2, and combining ANGPT2 antibodies with sorafenib restores sensitivity in RBMS3-deficient tumors 3. In triple-negative breast cancer, RBMS3 stabilizes PD-L1 mRNA through 3′-UTR binding to promote immune evasion; RBMS3 depletion combined with auranofin, an FDA-approved thioredoxin reductase inhibitor, enhances anti-tumor T-cell immunity 4. Beyond cancer, RBMS3 variants associate with exfoliation syndrome, a systemic extracellular matrix disorder 5, and with bone mineral density through gene–gene interactions 6.