The function of PENK (proenkephalin, ENSG00000181195) is as follows. [Met-enkephalin]: Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress. . [Leu-enkephalin]: Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress. . [Met-enkephalin-Arg-Phe]: Met-enkephalin-Arg-Phe neuropeptide acts as a strong ligand of Mu-type opioid receptor OPRM1. Met- enkephalin-Arg-Phe-binding to OPRM1 in the nucleus accumbens of the brain increases activation of OPRM1, leading to long-term synaptic depression of glutamate release. . [PENK(114-133)]: Increases glutamate release in the striatum and decreases GABA concentration in the striatum. . [Neuropeptide BAM22]: Neuropeptide that mediates stress- induced opioid analgesia (By similarity). Also possesses non-opioid action by acting as a ligand for MRGPRX1 receptor to induce itch in a histamine-independent manner (PubMed:11850634). . [Neuropeptide BAM8-22]: Neuropeptide that induces itch in a histamine-independent manner as well as nociceptive sensations (PubMed:11850634, PubMed:28223516). Acts as a ligand for MRGPRX1 receptor in sensory neurons of dorsal root ganglion: MRGPRX1-binding in the peripheral nervous system elicits itch and scratching, while MRGPRX1-binding in the central nervous system dampens chronic pain (PubMed:11850634, PubMed:21593341, PubMed:28223516, PubMed:36302898, PubMed:37591889, PubMed:39725036). {ECO:0000269|PubMed:11850634, ECO:0000269|PubMed:21593341, ECO:0000269|PubMed:28223516, ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37591889, ECO:0000269|PubMed:39725036}. [PENK(237-258)]: Increases glutamate release in the striatum. .