Npy1r, encoding the neuropeptide Y Y1 receptor, is a G protein-coupled receptor. Neuropeptide Y (NPY) binding to Npy1r is involved in multiple biological processes. NPY/Npy1r signaling is associated with pathways related to pain regulation, energy homeostasis, and cell growth regulation, among others. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been crucial for studying its functions [1-10].

In mouse models, conditional deletion of Npy1r from certain interneurons in the spinal dorsal horn affected neuropathic hypersensitivity, indicating that Grp/Npy1r-INs are key for neuropathic pain treatment [1]. In pancreatic cancer mouse models, pancreas-specific and whole-body knockout of Npy1r significantly decreased liver metastasis, showing that NPY/Npy1r signaling is an antimetastatic target [3]. Conditional inactivation of Npy1r in excitatory neurons of the brain limbic system in mice induced sex-related differences in metabolic and behavioral functions [2].

In conclusion, Npy1r is essential in regulating pain, energy metabolism, cell growth, and metastasis. Studies using KO and CKO mouse models have provided valuable insights into its role in neuropathic pain, pancreatic cancer, and sex-related metabolic and behavioral differences. These findings may contribute to the development of new therapeutic strategies for related diseases.