CPNE3 (copine 3) is a calcium-dependent phospholipid-binding protein that exhibits dual roles in cancer progression, with context-dependent tumor suppressive or oncogenic functions 1. In several cancer types, CPNE3 promotes tumorigenesis through distinct molecular pathways. In glioblastoma, CPNE3 upregulation enhances cell proliferation and inhibits apoptosis via PI3K/AKT pathway activation 1. In gastric cancer, CPNE3 creates a positive feedback loop with YAP1, inhibiting YAP1 ubiquitination and promoting transcription of downstream targets 2. CPNE3 also facilitates endometriosis malignant transformation through the miR-612/CPNE3 pathway 3. Conversely, in lung adenocarcinoma, CPNE3 functions as a tumor suppressor by regulating SQSTM1/p62 signaling and inhibiting epithelial-mesenchymal transition 4. Beyond cancer, CPNE3 plays important roles in pancreatic β-cell function, regulating glucose-stimulated insulin secretion and glucose uptake 5, and modulates the relationship between anxiety and working memory performance 6. Clinically, circulating exosomal CPNE3 serves as a diagnostic and prognostic biomarker for colorectal cancer 7, highlighting its potential therapeutic and diagnostic utility.