Persephin (PSPN) is a neurotrophic growth factor that exhibits dopaminergic and motor neuron survival activity 12. It functions as a ligand within the glial-cell-line-derived neurotrophic factor (GDNF) family, binding to its coreceptor GFRA4 and subsequently activating the RET receptor through autophosphorylation 1. Beyond its classical neuronal roles, PSPN participates in broader neuroprotective responses; following intracerebral hemorrhage, PSPN expression is upregulated as part of an anti-inflammatory program that promotes astrocyte phenotypic conversion toward neuroprotective A2 astrocytes 3. PSPN also functions in pain regulation, with differential expression across osteosarcoma cell types, suggesting involvement in cancer-associated pain processing 4. In intervertebral disc pathology, PSPN expression is significantly elevated in advanced degenerative stages and can be upregulated by inflammatory signals, implicating it in discogenic pain pathogenesis 5. These findings establish PSPN as a multifunctional neurotrophic factor with roles extending from neuronal survival to inflammation modulation and pain-related diseases, positioning it as a potential therapeutic target in neurodegenerative and inflammatory conditions.