CARMA proteins belong to the membrane-associated guanylate kinase-like (MAGUK) family of proteins that can function as molecular scaffolds that assist assembly of signal transduction molecules. CARMA1, CARMA2, and CARMA3 share high degrees of sequence and functional homology, but their tissue-specific distribution suggests that they serve distinct biological functions in different cell types. Both CARMA1 and CARMA3 associate with NEMO, the regulatory subunit of the IκK complex, thereby regulating activation of the NF-κB transcription factor. Also, gene inactivation studies showed a complete block in T and B cell immunity as well as an impaired response to LPS, indicating that CARMA1 is a critical regulator in both the adaptive and innate immune systems.