RAP1GDS1 encodes a guanine nucleotide exchange factor (GEF) that regulates multiple small GTPases involved in cellular signaling and trafficking. The protein functions as a GEF for prenylated RHOA and RHOC, facilitating their activation by promoting GDP-GTP exchange 1. RAP1GDS1 also serves as a chaperone for newly prenylated GTPases, guiding their downstream trafficking and processing 2, and escorts RAC1 to the nucleus 3. Disease associations have been established through genetic studies identifying RAP1GDS1 mutations in patients with intellectual disability, global developmental delay, and hypotonia, collectively termed Alfadhel syndrome 4. A homozygous splice acceptor mutation (1444-1G>A) causes aberrant splicing and decreased mRNA expression, leading to this neurodevelopmental phenotype 4. Additionally, RAP1GDS1 has oncogenic implications through chr4 translocations, particularly t(4;11)(q21;p15) that creates NUP98-RAP1GDS1 fusion proteins in T-cell acute lymphoblastic leukemia 56. These fusion events affect CD34+ hematopoietic precursors and represent a specific genetic abnormality in T-ALL 7. The protein is also expressed in various cancer types, including fibrosarcoma 8, highlighting its diverse roles in normal cellular function and disease pathogenesis.