TRPV3

TRPV3 (transient receptor potential vanilloid 3) is a non-selective cation channel that is highly expressed in epidermal keratinocytes and functions as an important regulator of skin physiology, particularly in thermosensation, epidermal homeostasis, and sensory signaling^[1][2]. Mechanistically, TRPV3 is activated by warm temperatures and mediates calcium influx, thereby coupling thermal stimuli to downstream cellular responses in keratinocytes^[2][3]. Activated keratinocytes can transmit temperature-related information to adjacent sensory neurons through ATP-dependent signaling, linking epidermal temperature detection to neural sensory pathways^[4][5]. Beyond thermosensation, TRPV3 participates in biological processes associated with itching, heat pain, hair development, skin regeneration, and inflammatory responses, highlighting its broad role in cutaneous biology^[1][6]. Disease-associated studies further demonstrate that TRPV3 mutations contribute to dermatological disorders, including atopic dermatitis and Olmsted syndrome, supporting its relevance as a disease-associated ion channel in skin pathology^[1]. Compared with related warm-sensitive isoforms such as TRPV4, TRPV3 exhibits distinct activation and sensitization properties and is notable for progressive sensitization following repeated stimulation, a characteristic considered unique among several TRP channels^[7][8]. This functional distinction has made TRPV3 a valuable model for investigating ion-channel gating mechanisms and epidermal sensory transduction^[7][8]. For experimental applications, both agonists and antagonists have been developed to modulate TRPV3 activity; however, currently available modulators generally show limitations in affinity or selectivity, motivating continued efforts toward pharmacological optimization and target validation^[8][9].