IL12RB1 encodes interleukin-12 receptor subunit beta 1, a critical component of cytokine signaling pathways essential for immune homeostasis. As a functional receptor subunit, IL12RB1 associates with IL12RB2 to form the high-affinity IL-12 receptor and with IL23R to form the IL-23 receptor, both mediating immune response through JAK-STAT signaling cascade activation 1. The gene undergoes allele-biased expression and produces alternatively spliced isoforms with distinct regulatory roles in IL-12 responsiveness 2. IL12RB1 is essential for T helper 1 and T helper 17 cell differentiation, including IL-12-driven T follicular regulatory cell development 3, and controls mycobacterial disease resistance 4. Mutations in IL12RB1 cause Mendelian susceptibility to mycobacterial diseases (MSMD), affecting 41% of reported MSMD patients with severe mycobacterial infections and high mortality 4. IL12RB1 polymorphisms show weak associations with pulmonary tuberculosis susceptibility 5 and Plasmodium vivax malaria 6. IL12RB1 is implicated in multiple autoimmune conditions including primary biliary cholangitis pathogenesis 1, and dysregulation contributes to inflammatory bowel disease susceptibility 7. The gene represents a key therapeutic target for immune-mediated disorders.