NGEF (neuronal guanine nucleotide exchange factor), also known as Ephexin1, is a Dbl family member that functions as a guanine nucleotide exchange factor (GEF) for Rho-type GTPases 1. In neurons, NGEF acts downstream of ephrin-EphA4 signaling to regulate axon guidance and growth cone dynamics by differentially activating RhoA, Rac1, and Cdc42 2. Upon EPHA4 activation, NGEF shifts GEF activity toward RhoA, promoting growth cone retraction 2. Beyond its canonical neuronal role, NGEF has emerged as a significant factor in cancer progression and neurological disease. In lung adenocarcinoma, elevated NGEF expression correlates with increased neural infiltration, larger tumor size, lymph node metastasis, and reduced overall survival through the Ephrin-A3/EphA2 pathway 34. High NGEF expression associates with enhanced sensitivity to certain chemotherapeutics and immunotherapy markers 4. Recently, NGEF was identified as a critical regulator of mTOR-dependent translation in cancer cells, promoting polysome formation and translation of TOP-motif containing genes, making it a potential synthetic lethal target for mTORC1 inhibitors 5. In Alzheimer's disease, NGEF neuronal knockdown impairs short-/intermediate-term memory function, implicating it in endosomal dysfunction-driven cognitive decline 6. Additionally, NGEF variants associate with idiopathic scoliosis through disrupted central pattern generator networks 2.