NRSN2 (neurensin-2) is a neuronal membrane protein with context-dependent roles in cancer biology. Originally annotated as potentially involved in vesicle maintenance and transport [UniProt], NRSN2 functions display cancer-type specificity. In gastric cancer, colorectal cancer, and breast cancer, NRSN2 is upregulated and promotes tumor progression through enhanced cell proliferation, migration, and invasion 123. In gastric cancer, NRSN2 overexpression correlates with poor prognosis, tumor grade, lymph node metastasis, and activates Wnt, p53, and NOD-like receptor signaling pathways 1. In colorectal cancer, NRSN2 interacts with SOX12 to facilitate malignant behaviors 2. Conversely, in hepatocellular carcinoma, NRSN2 functions as a tumor suppressor—decreased expression is found in 70.9% of cases and correlates with worse prognosis and larger tumor size 45. Loss of NRSN2 in HCC promotes proliferation via PI3K/AKT/mTOR and p53/p21 pathway dysregulation 5. In osteosarcoma, miR-488-3p suppresses malignant behaviors by targeting NRSN2 and promoting autophagy 6. Additionally, the NRSN2 antisense lncRNA (NRSN2-AS1) promotes ovarian cancer progression through PTK2/β-catenin and miR-744-5p/PRKX/Wnt signaling axes 78. NRSN2 represents a potential multi-cancer biomarker with tissue-specific prognostic significance.