Pleiotrophin (PTN) is a secreted heparin-binding growth factor that functions as a pleiotropic signaling molecule across multiple physiological systems 1. Primary functions include regulating cell proliferation, survival, differentiation, and migration through binding to cell-surface proteoglycan receptors (particularly PTPRZ1) and non-proteoglycan receptors like ALK and syndecan-2 2. PTN binds chondroitin sulfate groups on proteoglycans, inducing receptor clustering and oligomerization 1. This binding neutralizes negative charges on PTPRZ1, triggering receptor dimerization and inactivation of phosphatase activity, leading to increased tyrosine phosphorylation of substrates like ALK and CTNNB1, ultimately activating the PI3K-AKT and MAPK signaling pathways 3. In neural contexts, PTN promotes oligodendrocyte precursor differentiation, hippocampal neurogenesis, dendritic arborization, and spine development via AKT pathway activation 4. In testis, Leydig cell-derived PTN acts through SDC2 to regulate spermatogonial stem cell proliferation and self-renewal 5. Disease relevance includes major depressive disorder, where reduced astrocytic PTN-PTPRZ1 signaling in the prefrontal cortex contributes to depression-like responses 6, and schizophrenia, where PTN depletion in progenitors and neurons impairs neurogenesis and survival 7. Clinically, elevated PTN expression correlates with advanced cancer stage and poor overall survival across multiple tumor types 8, making PTN a potential prognostic biomarker and therapeutic target 3.