PTPN5 encodes striatal-enriched protein tyrosine phosphatase (STEP), a brain-specific phosphatase that plays critical roles in synaptic function and neuronal signaling. Mechanistically, PTPN5 dephosphorylates and inactivates mitogen-activated protein kinases (MAPKs) 1, as well as Src family kinases and NMDA receptors, thereby regulating synaptic plasticity and neuronal cell survival. PTPN5 also dephosphorylates Mob1a at the Y26 residue and is required for proper cytokinesis through regulation of this interaction 2. PTPN5 dysfunction is implicated in multiple neurological diseases. Genetic variants in PTPN5 associate with schizophrenia risk and impaired cognitive function, particularly attention performance 3. PTPN5 is involved in Alzheimer's disease pathogenesis related to tau protein lesions 4. In early-stage Alzheimer's disease, STEP61 (PTPN5 product) levels and activity increase initially but decrease with synaptic loss; conversely, tau pathology models show reduced STEP61 correlating with disease progression 5. A missense PTPN5 variant associates with decreased post-burn hypertrophic scarring severity, suggesting PTPN5's role in neuroinflammatory signaling 6. These findings establish PTPN5 as a promising therapeutic target for neurodegenerative and psychiatric conditions through restoration of tyrosine phosphorylation balance.