451 Modeling darier disease using gene-edited human keratinocytes and organotypic epidermis to identify therapeutic targets

Darier disease(DD) is a genetic disorder characterized by impaired intercellular adhesion and aberrant differentiation of keratinocytes, leading to hyperkeratotic papules and epidermal erosions. While mutations underlying DD are known to target SERCA2, an endoplasmic reticulum(ER) calcium pump, current therapies for this chronic, painful skin disorder are limited and some, such as oral retinoids, may pose significant long-term risks. Unfortunately, mice lacking SERCA2 do not replicate the cutaneous findings of DD seen in human patients.