TEN is considered when epidermal detachment exceeds 10–35% of the body surface area.2 Clinical trials with large patient numbers in TEN remain extremely challenging due to rapid disease evolution.3 Immediate supportive care in an intensive care setting is of major importance in the treatment of TEN.3 While it has been acknowledged that the reaction is caused by extensive keratinocyte (KC) cell death and a CD8+ T cell-driven response, the question of how to target the main drivers of cytotoxicity against the epidermis remained. Here, CALCA is linked to toxic epidermal necrolysis.