NRAS is a proto-oncogene encoding a small GTPase that functions as a molecular switch in cellular signaling by binding and hydrolyzing GDP/GTP 1. NRAS regulates multiple signaling cascades including the MAPK/ERK pathway and controls cell proliferation, differentiation, and membrane trafficking through its GTPase activity 2. Mechanistically, NRAS requires lipid modifications, particularly palmitoylation by ZDHHC9, for proper trafficking to the plasma membrane where it becomes activated and propagates downstream signals 2. Oncogenic NRAS mutations (primarily Q61R/K and codons 12/13) occur in 15-30% of melanomas and 48% of metastatic colorectal cancers, conferring constitutive activation 1, 3, 4. NRAS-mutant tumors display aggressive phenotypes and poor prognosis compared to wild-type counterparts, with resistance to conventional therapies 1. Mutant NRAS suppresses cGAS-STING antitumor immunity and evades immune surveillance 5. Therapeutically, MEK inhibitors combined with CDK4/6 inhibitors represent current standard approaches, while emerging strategies include STK19 inhibition, CK1δ-USP46 axis targeting, and SOS1 inhibition combined with STING agonists to restore antitumor immunity 1, 6, 3, 5. Despite advances, NRAS-mutant malignancies remain therapeutically challenging with significant unmet clinical needs.