Researchers have determined the structure of the TRPV1 ion channel at 3.4 Å resolution using electron cryo-microscopy, revealing its four-fold symmetry and the arrangement of transmembrane segments and domains. TRPV1, a member of the TRP family, is involved in sensing pain and temperature, and its structure provides insights into its function and regulation. The study highlights the role of the TRP domain in subunit assembly and allosteric modulation, as well as the interactions between the S4–S5 linker and other domains. The structure also shows a wide extracellular 'mouth' with a short selectivity filter, and the TRPV1 channel exhibits a unique architecture compared to voltage-gated channels. The findings demonstrate the power of cryo-EM in elucidating the structure of membrane proteins, offering a structural blueprint for understanding TRP channel function. The study also reveals the importance of TRPV1 in pain physiology and its potential as a target for analgesic drugs. The research underscores the significance of structural studies in understanding the diverse roles of TRP channels in cellular and environmental signaling.Researchers have determined the structure of the TRPV1 ion channel at 3.4 Å resolution using electron cryo-microscopy, revealing its four-fold symmetry and the arrangement of transmembrane segments and domains. TRPV1, a member of the TRP family, is involved in sensing pain and temperature, and its structure provides insights into its function and regulation. The study highlights the role of the TRP domain in subunit assembly and allosteric modulation, as well as the interactions between the S4–S5 linker and other domains. The structure also shows a wide extracellular 'mouth' with a short selectivity filter, and the TRPV1 channel exhibits a unique architecture compared to voltage-gated channels. The findings demonstrate the power of cryo-EM in elucidating the structure of membrane proteins, offering a structural blueprint for understanding TRP channel function. The study also reveals the importance of TRPV1 in pain physiology and its potential as a target for analgesic drugs. The research underscores the significance of structural studies in understanding the diverse roles of TRP channels in cellular and environmental signaling.