Dyclonine inhibition of TRPV3: From functional discovery to structural insight

•Yao and colleagues recently reported that the clinically approved local anesthetic dyclonine acts as a potent inhibitor of TRPV3, and identified several key residues in TRPV3 pore region that could toggle the inhibitory efficiency. The study by Neuberger et al. sheds light on the cryo-electron microscopy (cryo-EM) map of TRPV3–dyclonine complex, which reveals binding of the inhibitor within the channel pore. The allosteric binding site of dyclonine emerges as a potentially leverageable template for designing TRPV3-targeting drugs.