RALGPS1 (Ral GEF with PH domain and SH3 binding motif 1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RALA 1, contributing to intracellular signal transduction and potentially cytoskeletal organization. Unlike other RalGEFs such as RALGPS2, RALGPS1 silencing had minimal effects on lung cancer cell growth in vitro 1, suggesting a less critical role in NSCLC proliferation compared to related family members. Ralgps1 has emerged as a candidate gene in several cancer contexts through post-transcriptional regulation. In colorectal cancer, RALGPS1 was identified as a novel target of A-to-I RNA editing with subtype-specific signatures across consensus molecular subtypes 2. In uterine carcinosarcoma, aberrant alternative splicing of RALGPS1 (RALGPS1-87608-AT), regulated by splicing factor junction plakoglobin, showed significant association with distant metastasis and correlated with the pyrimidine metabolism pathway 3. RALGPS1 was also identified as a feature gene affecting skin cutaneous melanoma prognosis through alternative splicing events 4. Genetically, RALGPS1 deletions on chromosome 9.3 contribute to a contiguous gene deletion syndrome characterized by intellectual disability, developmental delay, microcephaly, and seizures of incomplete penetrance 5. A novel BCOR-RALGPS1 fusion has been identified in endometrial stromal sarcoma 6, and GTF2I::RALGPS1 fusion occurs rarely in phosphaturic mesenchymal tumors 7. Clinical significance of RALGPS1 dysregulation appears primarily through post-transcriptional and fusion-mediated mechanisms rather than its canonical GEF function.