SFMBT2 (Scm like with four mbt domains 2) is a chr10-associated protein that functions as a transcriptional repressor through histone binding and chr10 modification 1. The protein acts as a tumor suppressor in clear cell renal cell carcinoma, where its expression is decreased in advanced stages and associated with poor prognosis 1. SFMBT2 regulation involves post-translational modifications, with HDAC3-mediated deacetylation promoting SIAH1-controlled ubiquitination and proteasome degradation, particularly at lysine 687 1. In pediatric B-cell precursor acute lymphoblastic leukemia, SFMBT2 is among novel recurrently altered regions, with structural variants including fusion genes like SFMBT2::DGKD identified through optical genome mapping 2. The gene contains a large miRNA cluster in intron 10 that is unique to mice and rats, consisting of repeated B1 retrotransposons and microsatellites that contribute to species-specific miRNA evolution 3. Additionally, circular RNAs derived from SFMBT2 (circ-SFMBT2) play important regulatory roles in various cancers, including breast cancer where they promote tamoxifen resistance through ERα signaling 4, and in non-small-cell lung cancer where they are regulated by m6A methylation through YTHDF2 5.