Tenascin R (TNR) is a neural extracellular matrix glycoprotein with context-dependent roles in neuronal development and plasticity. TNR functions as a bidirectional regulator of cell adhesion and neurite outgrowth through interactions with distinct cell surface receptors. Binding to gangliosides inhibits integrin-mediated adhesion and FAK phosphorylation, promoting cell detachment [UniProt], while interaction with sulfatides supports oligodendrocyte adhesion and differentiation [UniProt]. TNR-CNTN1 interactions trigger neuronal repulsion and neurite outgrowth inhibition [UniProt]. TNR is a structural component of perineuronal nets, specialized extracellular matrix sheaths around certain neurons that regulate synaptic plasticity in the adult CNS 1. The adhesive properties of TNR are dynamically modulated by sulfated glycosaminoglycan additions, influencing developmental processes and synapse maintenance [UniProt]. Mutations in TNR are associated with neurodevelopmental disorder, non-progressive, with spasticity and transient opisthotonus. In CNS lesions, TNR's role in synaptic plasticity becomes particularly relevant for understanding recovery and neuroplasticity 1. These functions position TNR as a critical regulator of neural circuit formation and stability.