RALGDS (ral guanine nucleotide dissociation stimulator) is a 115 kDa guanine nucleotide exchange factor (GEF) located on chromosome 9.1 1 that functions as a critical regulator of Ras family signaling. As a GEF, RALGDS specifically promotes the conversion of inactive GDP-bound RalA and RalB to their active GTP-bound states 2, serving as a key effector that couples activated Ras to Ral signaling 3. The protein interacts with activated Ras and Rap1, positioning it as part of downstream signaling complexes 4. RALGDS contains a Ras Binding Domain (RBD) enabling Ras interaction and a REM-CDC25 homology region for its GEF activity 3. The RALGDS gene exhibits complex regulation, with at least 19 exons and two transcript variants of 4.0 kb and 6.0 kb, both ubiquitously expressed in human tissues 2. K-Ras dimerization can modulate RALGDS binding through conformational changes at the effector binding interface 5. In disease context, RALGDS expression is significantly upregulated by TGF-β signaling in systemic sclerosis dermal fibroblasts, suggesting involvement in pathological fibrosis 6. Additionally, RALGDS has been identified as a key protein in KRAS-associated cancer pathways, including pancreatic and colorectal cancers 7.