Caspase-14 (CASP14)

Caspase-14 is a unique, skin-specific member of the caspase family of cysteine-aspartic proteases, primarily expressed in the upper layers of the epidermis where it is crucial for skin barrier formation and terminal keratinocyte differentiation[1][2][3]. Unlike other caspases that mediate classical apoptosis, caspase-14 is activated during cornification—an alternative programmed cell death exclusive to the epidermis—and not involved in conventional apoptosis or inflammation[2][3]. Its primary biological role is the processing of (pro)filaggrin into filaggrin units and subsequently into free amino acids, which are key to maintaining stratum corneum hydration and effective protection from transepidermal water loss and UVB radiation damage[2][3]. Caspase-14 deficiency leads to impaired skin barrier structure and function, conferring increased sensitivity to environmental stresses and predisposing to skin diseases such as ichthyosis and atopic dermatitis[2][3]. Caspase-14 is regarded as a potential therapeutic target and biomarker for diseases manifesting abnormal epidermal differentiation or barrier function; however, there are currently no approved drugs that directly target this enzyme and its direct inhibition or activation in therapy remains experimental[2].

Other names

Caspase-14 subunit p17Caspase-14 subunit p10Caspase-14 subunit p20Caspase-14 subunit p8mini-ICEMICEARCI12apoptosis-related cysteine proteaseapoptosis-related cysteine peptidase