CPLX2 is a 134-amino acid protein encoded on chromosome 5.3 that regulates synaptic vesicle exocytosis and membrane fusion processes. At the presynaptic terminal, CPLX2 negatively regulates synaptic vesicle clustering at active zones while positively regulating late-stage exocytosis through SNARE complex interactions 1. The gene produces alternative transcripts with tissue-specific expression patterns across brain regions 1. Beyond its canonical synaptic role, CPLX2 exhibits context-dependent functions in disease. In glioma, CPLX2 acts as a tumor suppressor—downregulated expression correlates with higher grade and poorer prognosis, with CPLX2 overexpression impairing tumorigenesis through hypoxia and inflammation pathway regulation 2. CPLX2 knockdown enhances temozolomide resistance via miR-214-3p regulation 3. Conversely, in hepatocellular carcinoma, CPLX2 is significantly upregulated and predicts poor survival; knockdown promotes ferroptosis and apoptosis through NRF2 pathway inhibition and sensitizes cells to sorafenib 4. In colorectal cancer liver metastasis, CPLX2 is overexpressed and promotes progression via PI3K-AKT signaling 5. CPLX2 was identified as a Braak stage-associated hub gene in Parkinson's disease pathology 6 and negatively correlates with kidney stone risk 7. CPLX2 elevation in lung neuroendocrine tumors associates with poor survival and lymph vessel invasion 8.