RAPGEFL1 (Rap guanine nucleotide exchange factor like 1) is a probable guanine nucleotide exchange factor (GEF) localized to the plasma membrane with roles in Rap protein signal transduction and G protein-coupled receptor signaling 1. The gene functions in nervous system development and membrane-associated processes based on GO annotations. Mechanistically, RAPGEFL1 regulates the Rap signaling pathway, controlling cellular adhesion, migration, polarity, and metabolism to maintain cellular and tissue homeostasis 1. Its dysregulation impacts critical biological processes including cell cycle control and metabolic pathways such as thiamine and folate biosynthesis 1. RAPGEFL1 dysregulation is implicated in multiple malignancies. In thyroid cancer, RAPGEFL1 is upregulated through the LINC00162-miR-320A/miR-485 axis, promoting cancer progression 1. The gene was identified as a potential pathogenic driver in oral squamous cell carcinoma 2 and represents a biomarker in a nine-gene macrophage phenotype-related prognostic signature for pancreatic adenocarcinoma 3. RAPGEFL1 also shows copy number amplification in HER2-positive gastric cancer 4 and appears upregulated in melanoma with poor prognosis 5. Clinically, RAPGEFL1 serves as a therapeutic target in thyroid cancer and a prognostic biomarker in pancreatic cancer. Additionally, RAPGEFL1 was identified as a shared biomarker in concurrent metabolic dysfunction-associated steatotic liver disease and intervertebral disc degeneration, suggesting broader systemic disease involvement 6.