CARD11 is an adapter protein that plays a critical role in adaptive immune responses by transducing NF-κB activation downstream of T-cell receptor (TCR) and B-cell receptor (BCR) signaling 1. Upon TCR or BCR activation, CARD11 homooligomerizes to form a nucleating template that recruits BCL10 via CARD-CARD interactions, promoting BCL10 polymerization and subsequent MALT1 recruitment, ultimately leading to IKK phosphorylation and NF-κB nuclear translocation 1. Functionally, CARD11 is essential for constitutive NF-κB pathway activity and cell survival in activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL) 1. Disease-wise, CARD11 mutations are associated with hyper-IgE syndromes, characterized by atopic dermatitis, recurrent infections, and elevated IgE levels 234. CARD11 deficiency interrupts B-cell maturation and prevents transitional B-cell differentiation into marginal zone and follicular B cells 5. Clinically, CARD11 mutations in T-cell malignancies can enhance therapeutic T-cell efficacy, with CARD11-PIK3R3 fusions augmenting anti-tumor responses in immunotherapy models 6. Additionally, activating CARD11 mutations are found in adult T-cell leukemia/lymphoma, affecting T-cell receptor-NF-κB signaling pathways 7.