TRPV3, short for Transient Receptor Potential Vanilloid 3, is a Ca²⁺ -permeable nonselective cation channel and a member of the TRP superfamily [1,2,3]. It can recognize thermal stimulation (31-39 °C), playing a crucial role in temperature perception, pain transduction, skin physiology, inflammation, and cancer [1]. TRPV3 is highly expressed in skin keratinocytes and peripheral neurons, participating in Ca²⁺ homeostasis and signaling pathways related to itch, dermatitis, hair growth, and skin regeneration [2].

Gain-of-function genetic mutations of TRPV3 in rodents and humans have been key in revealing its critical role in skin health and disease [3]. For instance, in Trpv3+/G568V mice (a gain-of-function model), TRPV3-activated PARP1/AIFM1/MIF axis through oxidative stress contributes to atopic dermatitis, with keratinocytes undergoing parthanatos, an underestimated form of cell death in skin diseases [4]. In acne-like mice, TRPV3 expression increased in skin lesions, and its activation promoted sebocyte inflammation via transcriptional modulating TLR2, exacerbating acne-related inflammation [5].

In conclusion, TRPV3 is essential for various physiological functions, especially in the skin. Studies using genetic mouse models, such as those with gain-of-function mutations, have significantly contributed to understanding its role in diseases like atopic dermatitis and acne, providing potential therapeutic targets for these skin conditions.