SART3 (spliceosome associated factor 3, U4/U6 recycling protein) is an RNA-binding protein that functions primarily in RNA splicing and spliceosome assembly. The protein serves as a reader of symmetrically dimethylated arginine (SDMA)-marked glycine- and arginine-rich motifs through its HAT (half-a-tetratricopeptide) repeat domains, which is essential for recognizing proteins like fibrillarin and coilin 1. SART3 plays crucial roles in spliceosome recycling and RNA processing, with its dysfunction causing aberrant splicing patterns 2. Beyond splicing, SART3 promotes homologous recombination DNA repair by facilitating DNA-RNA hybrid removal and enhancing DNA end resection through interactions with DDX1 helicase and the USP15-BARD1 pathway 3. Clinically, biallelic SART3 variants cause a spliceosomopathy termed INDYGON syndrome, characterized by intellectual disability, neurodevelopmental defects, and gonadal dysgenesis in 46,XY individuals 2. SART3 is also recognized as a tumor-associated antigen, with elevated expression in various cancers including hepatocellular carcinoma and breast cancer, where it correlates with poor prognosis and can induce cytotoxic T lymphocyte responses 45. The protein's involvement in cancer stemness through CD44 alternative splicing regulation further underscores its clinical significance 6.