Caspase recruitment domain-containing protein 14 (CARD14)

Caspase recruitment domain-containing protein 14 (CARD14) is a multidomain scaffold protein in the membrane-associated guanylate kinase (MAGUK) family, predominantly expressed in epithelial cells, particularly keratinocytes[1][3][8]. CARD14 contains a caspase recruitment domain (CARD), a coiled-coil region, an inhibitory domain, and a C-terminal MAGUK module. It forms part of a signalosome complex with BCL10 and MALT1, facilitating activation of the NF-κB and p38/JNK MAP kinase pathways, which are critical for inflammatory and immune gene expression, cell survival, and proliferation[1][3][7]. Gain-of-function mutations in CARD14 disrupt autoinhibition and drive constitutive NF-κB signaling, leading to pro-inflammatory cytokine overproduction characteristic of psoriasis and related skin conditions[1][2][5][8]. In addition to its roles in skin inflammation, CARD14 expression is observed in various cancers and may serve as a prognostic marker or modulator of tumor microenvironment and immune cell infiltration[4]. No drugs directly inhibit CARD14, but therapies targeting its downstream pathways (NF-κB, mTOR) are clinically relevant in managing associated diseases[1][4][5].

Other names

Caspase recruitment domain-containing protein 14CARMA2Carma 2BIMP2CARD-containing MAGUK protein 2PRPPSORS2PSS1bcl10-interacting MAGUK protein 2

Inhibition of downstream NF-κB pathway signaling; suppression of inflammatory gene expression; blockade of mTOR signaling[1][5].