The study by Liao et al. determines the structure of the TRPV1 ion channel, a member of the transient receptor potential (TRP) family, using electron cryo-microscopy at 3.4 Å resolution. TRPV1 is a mammalian TRP channel that responds to a wide range of chemical and physical stimuli, including capsaicin and heat. The structure reveals that TRPV1 has a four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 and the intervening pore loop, flanked by S1–S4 voltage-sensor-like domains. The extracellular 'mouth' of TRPV1 is wide with a short selectivity filter. The conserved 'TRP domain' interacts with the S4–S5 linker, contributing to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. This study provides a structural blueprint for understanding the unique aspects of TRP channel function and highlights the importance of TRP channels in various biological processes and disorders.The study by Liao et al. determines the structure of the TRPV1 ion channel, a member of the transient receptor potential (TRP) family, using electron cryo-microscopy at 3.4 Å resolution. TRPV1 is a mammalian TRP channel that responds to a wide range of chemical and physical stimuli, including capsaicin and heat. The structure reveals that TRPV1 has a four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 and the intervening pore loop, flanked by S1–S4 voltage-sensor-like domains. The extracellular 'mouth' of TRPV1 is wide with a short selectivity filter. The conserved 'TRP domain' interacts with the S4–S5 linker, contributing to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. This study provides a structural blueprint for understanding the unique aspects of TRP channel function and highlights the importance of TRP channels in various biological processes and disorders.