IFNL2 (interferon lambda 2) is a type III interferon cytokine that plays a critical role in antiviral defense, particularly at epithelial barriers 1. IFNL2 functions as a ligand for the IL10RB/IFNLR1 receptor heterodimer, activating JAK/STAT signaling to induce interferon-stimulated genes (ISGs) that establish an antiviral state 2. Its epithelial cell-restricted expression pattern and receptor distribution limit its activity primarily to epithelial tissues, including skin, respiratory, and gastrointestinal tracts 3. In HSV skin infections, IFNL2 restricts lesion severity without reducing viral loads by suppressing neutrophil-mediated pathology through reduced CXCL9-dependent recruitment 3. IFNL2 expression is enhanced during poly(I:C)-stimulated antiviral responses in intestinal epithelial cells 4 and is downregulated in congenital Zika syndrome placentas, suggesting insufficient type III IFN contributes to adverse outcomes 5. Clinically, elevated endogenous IFNL2 expression serves as an independent prognostic marker associated with poor cancer prognosis, where it may promote tumor progression through JAK-STAT pathway activation alongside T-cell dysfunction 6. IFNL2 also suppresses influenza viral gene expression induction 7. Emerging evidence indicates potential autoantibody responses to IFNL2 in certain neuropathies, though clinical significance remains unclear 8.