PIRT is a 137 amino acid multi-pass membrane protein. Highly conserved among vertebrates, PIRT consists of two transmembrane domains and one putative C-terminal phosphoinositide-binding domain. Although PIRT is expressed in peripheral nervous system, with highest levels in dorsal root ganglion and trigeminal neurons, and lowest levels in sympathetic and enteric neurons, it is not expressed in spinal cord. PIRT is a required component of the VR1 complex, which positively regulates VR1, a sensor of both noxious heat and capsaicin. Correspondingly, PIRT knockout results in impaired responses to noxious heat and capsaicin exposure, while VR1 remains unaltered. The gene that encodes PIRT maps to human chromosome 17p13.1.