IFNLR1 encodes the interferon lambda receptor 1, which forms a heterodimeric receptor complex with IL10R2 to mediate type III interferon signaling 1. This receptor binds interferon lambda ligands (IFNL2/IFNL3) and activates the JAK/STAT signaling pathway, leading to expression of interferon-stimulated genes that contribute to antiviral defense 1. IFNLR1 exhibits tissue-specific expression patterns, primarily in epithelial cells of respiratory, gastrointestinal, and reproductive tracts, thereby limiting type III interferon responses to these tissues 1. Multiple IFNLR1 isoforms exist with distinct functional properties - isoform 1 supports full canonical signaling, while isoforms 2 and 3 show altered signaling capacity and can modulate cellular responses to interferons 2. Disease associations include roles in immune evasion of squamous cell carcinomas through epigenetic silencing 3, susceptibility to hepatitis C virus infection 4, and association with psoriatic arthritis risk 5. Genetic variants in IFNLR1 have been linked to breast cancer protection 6 and hypertension through smoking-mediated pathways 7. A structural variant disrupting an IFNLR1 enhancer contributes to psoriasis susceptibility 8, highlighting the clinical significance of this receptor in immune-mediated diseases.