RASGRP3 is a guanine nucleotide exchange factor (GEF) that activates Ras family proteins (H-Ras, R-Ras, and Rap1) downstream of diacylglycerol and calcium signaling 1. It functions as a molecular switch in phosphoinositide-mediated signal transduction, particularly in response to growth factors like VEGF, HGF, and EGF 2. RASGRP3 promotes MAPK and PI3K/AKT pathway activation, leading to increased cell proliferation and survival 3. RASGRP3 is aberrantly overexpressed across multiple human malignancies, including breast cancer, melanoma, and esophageal squamous cell carcinoma, where it drives oncogenic signaling 324. In uveal melanoma, RasGRP3 is specifically required for GNAQ/GNA11-driven Ras activation and tumorigenesis, identifying it as a critical signaling node in this disease 5. In oxaliplatin-resistant colorectal cancer, RASGRP3 upregulation via the AC092894.1/USP3/AR axis promotes chemoresistance and MAPK pathway activation 6. Clinically, RASGRP3 suppression reduces tumor growth, cell proliferation, invasion, and sensitizes cancer cells to chemotherapy in preclinical models 32. Additionally, RASGRP3 expression associates with lung function traits, suggesting broader biological significance beyond cancer 7. These findings position RASGRP3 as a potential therapeutic target across multiple cancer types.