IL10RB encodes a shared cell surface receptor subunit required for signaling by multiple class 2 cytokines including IL-10, IL-22, IL-26, IL-28, and type III interferons 1. The protein functions as a co-receptor that activates JAK-STAT signaling pathways upon ligand binding, leading to expression of interferon-stimulated genes and antiviral responses. In intestinal biology, IL10RB is essential for IL-22-mediated Paneth cell formation and antimicrobial peptide expression, with IBD-associated loss-of-function mutations abolishing Paneth cell development 1. The receptor plays critical roles in immune regulation, as IL10RB signaling maintains functional PD-1int TCF-1+ CD8+ T cells and prevents T cell exhaustion in cancer models 2. Clinically, IL10RB variants are associated with severe COVID-19 susceptibility, likely through impaired interferon signaling 3, and autoimmune conditions including systemic lupus erythematosus 4. Biallelic loss-of-function mutations cause infant-onset inflammatory bowel disease (IBD25), demonstrating the gene's essential role in maintaining intestinal immune homeostasis 5. The gene's expression is regulated by transcription factors Sp8 and Sp9, and is elevated in Alzheimer's disease brains 6.