DPYSL5 (dihydropyrimidinase-like 5) is a cytosolic phosphoprotein that plays critical roles in neuronal development and brain formation. Primary function: DPYSL5 mediates negative regulation of dendrite morphogenesis and axonal guidance through interactions with cytoskeleton-associated proteins, particularly MAP2 and β-tubulin 1. Mechanism: DPYSL5 functions as an intracellular mediator of neurotrophic factor signaling, regulating dendritic arborization, axonal elongation, and synaptic density during early brain development 2. In cancer contexts, DPYSL5 promotes cellular plasticity via EZH2-mediated PRC2 activation, driving neuroendocrine transformation in prostate cancer 3. Disease relevance: De novo missense variants in DPYSL5 cause neurodevelopmental disorders with brain malformations, including corpus callosum agenesis and cerebellar abnormalities 14. These variants impair dendritic outgrowth and synaptic development, resulting in developmental delay and intellectual disability 4. DPYSL5 mutations are associated with Ritscher-Schinzel syndrome 4, a rare genetic condition characterized by craniofacial dysmorphism and neurological abnormalities 5. Clinical significance: DPYSL5 represents a key regulator of brain development and is increasingly recognized as important in both neurodevelopmental pathology and neoplastic transformation, suggesting therapeutic potential in both developmental and oncological contexts.