Targeting NLRP10 in Atopic Dermatitis: An Emerging Strategy to Modulate Epidermal Cell Death and Barrier Function

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, characterized by pruritic and eczematous lesions. Skin barrier dysfunction and aberrant inflammatory responses are hallmark features of AD. Recent genome-wide association studies have implicated NLRP10, a unique member of the NOD-like receptors (NLRs) lacking a leucine-rich repeat (LRR) domain, in AD susceptibility. Unlike other NLRs, the physiological role of NLRP10 in skin remains incompletely understood. Emerging evidence shows that NLRP10 regulates keratinocyte survival and differentiation, acts as a molecular sensor for mitochondrial damage, enhances anti-microbial response and contributes to skin barrier function. This review summarizes current insights into NLRP10′s functions in skin homeostasis, its interplay with cell death pathways, and its role in maintaining skin barrier function. Furthermore, therapeutic opportunities to target NLRP10 as a novel strategy for modulating epidermal cell death and restoring barrier function in AD are highlighted.