LRRC31 (leucine-rich repeat-containing protein 31) is a multifunctional protein with distinct roles in cancer biology and epithelial homeostasis. In breast cancer brain metastasis, LRRC31 functions as a DNA repair suppressor by interacting with Ku70/Ku80 and the ATR protein complex, inhibiting DNA-PKcs recruitment and disrupting the MSH2-ATR module, thereby sensitizing tumors to radiation therapy 1. Conversely, in colorectal cancer, LRRC31 expression is downregulated and correlates with tumor progression, microsatellite status, and poor prognosis, suggesting a tumor-suppressive role 2. In eosinophilic esophagitis, IL-13 induces LRRC31 expression, which enhances epithelial barrier function and suppresses kallikrein serine protease expression 3. LRRC31 has been identified as a circulating biomarker component in a five-gene model predicting infliximab response in rheumatoid arthritis 4, and genetic variants in LRRC31 associate with telomere length and Type 2 Diabetes susceptibility 5, 6. These findings establish LRRC31 as a context-dependent regulator with potential therapeutic relevance across multiple disease domains.