IFNL1 (interferon lambda 1) is a type III interferon with critical antiviral and immunomodulatory functions, predominantly active in epithelial tissues. It acts as a ligand for the heterodimeric receptor composed of IL10RB and IFNLR1, triggering JAK/STAT signaling to induce expression of interferon-stimulated genes that establish an antiviral state. Its cell-type selectivity reflects the epithelial-restricted expression of its receptor IFNLR1. Beyond antiviral defense, IFNL1 upregulates MHC class I antigen expression and promotes regulatory T cell differentiation while suppressing type 2 immune responses. In alveolar macrophages infected with Mycobacterium tuberculosis, IFNL1 is specifically and highly upregulated compared with monocyte-derived macrophages, contributing to the type I and II interferon response 1. Recent work demonstrates that ATG10S promotes IFNL1 expression and facilitates autophagic degradation of viral proteins from diverse viruses 2. Emerging therapeutic applications include engineered probiotics secreting IFNL1 to reduce intestinal inflammation in inflammatory bowel disease models 3, and photochemotherapy activation of IFNL1 via the STING-cGAS pathway in cutaneous T-cell lymphoma 4. Genetic variation in IFNL1, specifically the rs30461 polymorphism, associates with COVID-19 severity risk 5. These findings position IFNL1 as a promising target for antiviral and immunomodulatory therapeutics.