NPVF (neuropeptide VF precursor) encodes RF-amide peptides that function as endogenous ligands for neuropeptide FF receptor 1 (NPFFR1), a G-protein coupled receptor 1. The NPVF/NPFFR1 system exhibits distinct tissue-specific roles: in the central nervous system, NPVF-derived peptides potently attenuate morphine-induced analgesia via NPFFR1, functioning as part of an endogenous anti-opioid mechanism 2. In peripheral tissues, NPVF promotes bone regeneration by activating NPFFR1 in endothelial cells to enhance angiogenesis through miR-181c-3p upregulation and AGO1 downregulation, while simultaneously promoting osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling 3. NPVF is also expressed during primate retinal development, where it localizes to macular Müller glia cells and may contribute to foveal specialization 4. Beyond bone and nervous system, NPVF and NPFFR1 regulate energy homeostasis, nociception, and reproduction 5. Genetic polymorphisms in NPVF (rs12700667) have been associated with endometriosis-related infertility 6. The structural basis of NPVF-NPFFR1 selectivity involves C-terminal RF-amide interactions and N-terminal variations, distinct from NPFF-NPFFR2 interactions 1.