IL12RB2 encodes the interleukin-12 receptor subunit beta 2, a signaling component of the IL-12 receptor that couples to the JAK2/STAT4 pathway to promote T cell and NK cell proliferation and drive T helper 1 (Th1) differentiation through enhanced interferon-gamma production. Beyond canonical immune signaling, IL12RB2 demonstrates broader biological relevance: it is expressed in both hematopoietic cells and interfollicular keratinocytes, where IL-12 signaling protects skin barrier integrity and suppresses hyperproliferation 1. IL12RB2 expression is dysregulated in multiple inflammatory and autoimmune conditions. In systemic lupus erythematosus, IL12RB2 expression is significantly downregulated in CD4+ T cells, suggesting impaired Th1 responses 2. IL12RB2 genetic variants are recognized susceptibility factors for several diseases: Behçet's disease 3 4, myasthenia gravis 5, and lung adenocarcinoma, where reduced IL-12 signaling activity predisposes to disease 6. Additionally, IL12RB2 transcript levels are significantly elevated in idiopathic multicentric Castleman disease subtypes associated with worse outcomes, potentially contributing to cytokine storm pathology 7. The IL12RB2/TNFRSF8 expression ratio has diagnostic value for oral lichen planus 8. These findings establish IL12RB2 as a critical regulator of adaptive and innate immunity with substantial clinical implications across multiple disease contexts.