Caspase recruitment domain family member 18 (CARD18)

Caspase recruitment domain family member 18 (CARD18), also known as ICEBERG, is a member of the death-domain-fold superfamily and contains a caspase recruitment domain (CARD) but little else structurally[1][3][4]. CARD18 is primarily expressed in keratinocytes, particularly in the granular layer of human epidermis, and is induced by proinflammatory stimuli and ultraviolet (UV) stress[2]. It functions as a negative regulator of the inflammasome: it binds caspase-1 via CARD-CARD interactions, thereby inhibiting caspase-1-mediated interleukin-1β (IL-1β) activation and release, a central pathway in inflammation[2][3][4]. As a CARD-only protein (COP), it acts as a pseudo-substrate or inhibitor, preventing caspase-1 from associating with the adaptor protein RIP2 and participating in downstream proinflammatory signaling complexes[1][5]. Loss of CARD18 expression has been observed in the lesional epidermis of patients with lichen planus, suggesting a role in skin inflammatory diseases[2]. CARD18 has potential relevance for diseases where dysregulation of IL-1β and the inflammasome are implicated, such as certain cancers and chronic inflammatory disorders[3][4]. However, there are currently no approved drugs known to specifically target this protein.

Other names

Caspase recruitment domain-containing protein 18ICEBERGpseudo-ICECaspase-1 inhibitor IcebergUNQ5804UNQ5804/PRO19611ICEBERG caspase-1 inhibitor

Inhibits caspase-1-mediated activation of pro-inflammatory cytokine IL-1β by directly binding to caspase-1 and preventing its association with RIP2