CDC42EP3 (CDC42 effector protein 3) is a key cytoskeletal regulatory protein that coordinates actin and septin networks downstream of the small GTPase CDC42. CDC42EP3 directly binds to septins, actin filaments, and actin monomers, with septin-bound CDC42EP3 accelerating actin filament polymerization 1. The protein plays a critical role in cellular mechanotransduction by sensitizing fibroblasts to mechanical cues and enabling the emergence of cancer-associated fibroblasts (CAFs) through coordination of actin and septin networks 2. CDC42EP3 function requires tight regulation by CDC42, and its expression precedes the highly contractile phenotype characteristic of activated fibroblasts 3. In cancer contexts, CDC42EP3 acts as a tumor promoter across multiple cancer types including gliomas, osteosarcoma, and gastric cancer, where it promotes cell proliferation, migration, and tumor growth while inhibiting apoptosis 456. The protein regulates oncogenic pathways including CCND1 expression through c-Myc-mediated transcription in gliomas and modulates PI3K/AKT/mTOR signaling in osteosarcoma 45. Additionally, overactivated CDC42 acting through CDC42EP3 can trigger DNA damage response signaling, sensitizing cells to genotoxic stress 7. CDC42EP3 has emerged as a potential therapeutic target for various cancers and intervertebral disc degeneration 8.