RAP1GAP is a GTPase-activating protein that negatively regulates RAP1, a small G protein involved in cellular signaling 1. By converting active GTP-bound RAP1 to its inactive GDP-bound state, RAP1GAP functions as a critical regulator of the RAP1/MAPK/ERK signaling pathway 2. RAP1GAP expression is frequently downregulated in human tumors, with loss of function impairing cell-cell adhesion through altered adherens junction protein distribution and enhanced integrin-dependent cell-matrix interactions 3. In differentiated thyroid cancer, RAP1GAP functions as a tumor suppressor, with its inactivation occurring via DNA hypermethylation of regulatory CpG islands 4. Beyond cancer, RAP1GAP is essential for neuronal function; TDP-43 loss induces cryptic splicing and downregulation of RAP1GAP, directly impairing neuronal excitability and synaptic transmission in amyotrophic lateral sclerosis and frontotemporal dementia 5. In endometriosis, n-butyrate treatment reduces lesion growth through RAP1GAP signaling 6. As a component of prognostic gene signatures in pancreatic cancer 7 and bladder cancer, where it correlates with immune cell infiltration patterns 8, RAP1GAP represents both a tumor suppressor and potential immunotherapeutic target across multiple malignancies.