TRPV3 is a calcium-permeable nonselective cation channel widely expressed in skin keratinocytes and epithelial tissues 1. Primary function: TRPV3 acts as a temperature sensor, activated by innocuous warm temperatures (31-39°C) and noxious heat above 39°C, with activation exhibiting outward rectification 12. The channel pore can dilate to accommodate larger cations 1. Mechanism: TRPV3 activation triggers calcium influx that engages downstream signaling pathways. Intracellularly, accumulated farnesyl pyrophosphate (an endogenous ligand) binds TRPV3's intracellular domains, activating calmodulin-calcineurin-NFAT and PYK2-RAS-ERK pathways 3. TRPV3 also negatively regulates hair growth through keratinocyte proliferation suppression and hair follicle apoptosis 1. Disease relevance: Gain-of-function TRPV3 mutations cause Olmsted syndrome and focal palmoplantar keratoderma through TRPV3-mediated parthanatos (calcium-dependent oxidative stress-induced cell death) and PARP1/AIFM1 axis activation 4. TRPV3 activation contributes to atopic dermatitis pathogenesis via keratinocyte inflammatory mediator secretion and immune cell infiltration 54. Clinical significance: TRPV3 antagonists represent viable therapeutic targets; selective TRPV3 inhibitors like Scutellarein ameliorate dermatitis in mouse models 6.