RAP1B is a small GTPase that plays critical roles in endothelial function, immune regulation, and platelet biology. As a member of the RAS oncogene family, RAP1B possesses intrinsic GTPase activity and regulates multiple cellular processes through GTP/GDP cycling 1. In endothelial cells, RAP1B serves as a key regulator of VEGFR2 signaling, promoting angiogenesis and nitric oxide production while mediating vascular immunosuppression in tumors 12. The protein functions through downstream effector interactions, with distinct roles from its closely related isoform RAP1A 1. RAP1B also participates in immune regulation, where it acts in the IFITM2-RAP1B-ERK signaling pathway to promote regulatory T cell differentiation during sepsis-induced immunosuppression 3. In platelets, RAP1B rapidly associates with the cytoskeleton upon thrombin activation, contributing to platelet function 4. Disease relevance includes its role as a novel pan-extracellular vesicle marker in cancer diagnostics 5 and its overexpression in various malignancies affecting proliferation, metastasis, and treatment resistance 6. Clinically, heterozygous variants disrupting RAP1B GTPase activity cause syndromic thrombocytopenia with congenital malformations and neurological features 7, establishing RAP1B as a disease gene with therapeutic potential in vascular pathologies and cancer.