Figure 2: Representative pathways and mechanisms involved in the pathogeneses of AiKDs. (a) Excessive activation of the IL-36 pathway in pustular psoriasis: IL36RN loss-of-function variants result in insufficient inhibition of IL-36 signaling, leading to downstream inflammatory responses and excessive chemokine/cytokine production. (b) Hyperactivation of the CARD14-NFkB pathway in pustular psoriasis and PRP type V: CARD14 gain-of-function variants hyperactivate NFkB, resulting in excessive immune responses and chemokine/cytokine secretion. (c) Continuous activation of the NLRP1 inflammasome pathway in FKLC: NLRP1 gain-of-function variants make constitutively activated NLRP1 inflammasomes in keratinocytes, leading to the upregulated secretion of IL-1β and IL-18. (d) Hyperactivation of the JAK1-STAT pathway in AiKD with hepatitis and autism: A gain-of-function variant of JAK1 activates STATS excessively, resulting in the upregulation of inflammatory responses and in increased chemokine/cytokine production. Red up arrows: Upregulation. Blue arrows: Activation, binding or secretion. ⊥: Inhibition. AiKD: Autoinflammatory keratinization disease, GPP: Generalized pustular psoriasis, PRP: Pityriasis rubra pilaris, IL: Interleukin.