SRPX2 (sushi repeat containing protein X-linked 2) encodes a secreted glycoprotein that plays critical roles in neuronal development and synaptogenesis. The protein acts as a synaptogenic factor that specifically promotes excitatory synapse formation in the cerebral cortex, with SRPX2 knockout mice showing reduced VGlut2 excitatory synapses while VGlut1 and inhibitory synapses remain largely unaffected 1. SRPX2 functions downstream of the FoxP2 transcription factor, which regulates SRPX2 expression levels to modulate synapse formation 2. The protein contains sushi repeat domains and acts as a ligand for the urokinase plasminogen activator surface receptor, participating in cellular processes including migration, adhesion, and angiogenesis. Beyond synaptogenesis, SRPX2 is involved in stem cell differentiation through the calcineurin A gamma/NFATc3/SRPX2 signaling axis 3 and plays roles in pathological processes, including fibroblast-to-myofibroblast transition in pulmonary fibrosis 4 and autophagy-mediated chemoresistance in colorectal cancer 5. Clinically, SRPX2 mutations are associated with X-linked developmental disorders including Rolandic epilepsy, intellectual disability, and speech dyspraxia 6. The gene has undergone human-specific evolution, with a fixed R75K substitution in the functional sushi domain since the human-chimpanzee split 7, highlighting its potential importance in human brain development and language circuits.