CRIP2 (cysteine-rich protein 2) is a multifunctional zinc-binding protein with diverse roles in vascular development, cellular homeostasis, and cancer progression. Structurally, CRIP2 belongs to the conserved Lin-1/Isl1/Mec3 double zinc finger family 1 and exhibits protein-binding capacity with cytoskeletal and signaling proteins 2. Primary Function: CRIP2 regulates vascular development through modulation of endothelial cell adhesion, migration, and proliferation 2. It interacts with cytoskeletal proteins KRT8 and VIM to fine-tune cytoskeleton formation and controls the VEGFA/CDC42 signaling pathway 2. Additionally, CRIP2 functions as a nuclear copper-binding protein that suppresses autophagy activation through copper-mediated proteasomal degradation 3. Disease Relevance: CRIP2 dysregulation associates with multiple malignancies. In non-small cell lung cancer, elevated CRIP2 correlates with radioresistance and poor prognosis 4. In breast cancer, miR-449a and miR-6767-5p suppress CRIP2 expression, promoting proliferation, migration, and invasion via NF-κB pathway activation and epithelial-mesenchymal transition 56. CRIP2 represents a prognostic biomarker in colon cancer CAF-related signatures associated with therapeutic resistance 7. Clinical Significance: CRIP2 serves as a potential therapeutic target for improving radiotherapy efficacy and overcoming cancer progression through targeted modulation of copper metabolism and NF-κB signaling pathways.