A unifying molecular mechanism underlying the association of CARD14 alleles with autoinflammatory and T-cell mediated skin disorders

The CARD14 (Caspase Recruitment Family Member 14) locus encodes a scaffold protein that mediates NF-kB signalling in keratinocytes and is therefore crucial to the maintenance of skin immune homeostasis. In keeping with this notion, gain-of-function CARD14 mutations have been observed in patients with plaque psoriasis and pityriasis rubra pilaris, two skin disorders mediated by abnormal T cell activation. More recently, a CARD14 missense variant has been tentatively associated with generalised pustular psoriasis (GPP), an auto-inflammatory condition characterised by acute episodes of skin pustulation and systemic upset.