IL10RA encodes the alpha subunit of the interleukin-10 receptor, which plays a crucial role in anti-inflammatory signaling. Upon IL-10 binding, IL10RA undergoes conformational changes that facilitate heterotetrameric complex formation with IL10RB, activating JAK1 and TYK2 kinases 12. This leads to STAT3 phosphorylation, nuclear translocation, and transcription of anti-inflammatory genes, while also inhibiting starvation-induced autophagy 3. IL10RA deficiency is strongly associated with very early-onset inflammatory bowel disease (VEO-IBD), particularly prevalent in East Asia, characterized by refractory diarrhea, severe perianal disease, and high mortality rates 45. The gene shows complex inheritance patterns, including compound heterozygous mutations and large deletions that require careful genetic analysis for accurate diagnosis 5. IL10RA expression is regulated by transcription factors Sp8 and Sp9, and is elevated in Alzheimer's disease brain tissue 6. The receptor also plays roles in cancer biology, where IL-10 signaling through IL10RA on myeloid cells and regulatory T cells promotes colorectal cancer lung metastasis 7. Genetic polymorphisms in IL10RA are associated with systemic lupus erythematosus susceptibility and may serve as biomarkers in chr11 rhinosinusitis with nasal polyps 89.