Selectively activates the heat-activated TRPV1 channel. It binds to TRPV1 in an open state-dependent manner, trapping it there to produce irreversible currents (PubMed:20510930, PubMed:26880553, PubMed:27281200). It binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer (PubMed:26880553, PubMed:27281200). It also partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning (K1) and channel activation (K2) (PubMed:26880553). In addition, the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation (PubMed:26880553). Interacts with TRPV1 (2 toxins (4 moieties) bind 1 channel (homotetramer)). Expressed by the venom gland. The presence of 'disulfide through disulfide knots' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots' that are separated by a short linker. Bivalence accounts for irreversible toxin action. Belongs to the neurotoxin 23 family. Double-knot toxin subfamily.