Epidermal keratinocytes are key for maintenance of the integrity of the epidermis. One of the main drivers of keratinocyte differentiation is the calcium gradient; calcium concentration gradually increases towards the outer layers of the epidermis. Atopic dermatitis (AD) is a disorder associated with a chronic inflammatory state and a compromised epidermal barrier. Keratinocytes secrete lipid-rich small extracellular vesicles (sEVs) that acts as mediators of both local and long-distance signaling.