SEMA4F encodes a transmembrane semaphorin that functions as a cell surface receptor regulating multiple aspects of neural development and pathology. The protein primarily controls oligodendrocyte precursor cell migration and differentiation in the developing brain 1. SEMA4F is expressed by neurons throughout neural development and in the adult brain, with preferential postsynaptic dendritic localization, and interacts with the synaptic scaffolding protein SAP90/PSD-95 at glutamatergic synapses 21. In Schwann cells, SEMA4F mediates axonal contact, with its downregulation disrupting Schwann cell-axonal interactions and promoting cell proliferation, contributing to neurofibroma development in neurofibromatosis type 1 3. In cancer contexts, SEMA4F plays critical roles in tumor progression: it drives glioblastoma infiltration through activity-dependent mechanisms involving bidirectional tumor-neuron signaling and synaptic remodeling 45, and promotes breast cancer axonogenesis and metastasis through TGFβ-induced expression 6. SEMA4F has been identified as a potential biomarker associated with poor survival outcomes in glioblastoma patients 7, highlighting its clinical significance in cancer prognosis and potential therapeutic targeting.