LRFN2 is a synaptic adhesion molecule with dual roles in neural and non-neural tissues. In the nervous system, LRFN2 functions as a core component of excitatory synapse maturation, promoting neurite outgrowth in hippocampal neurons 1 and enhancing cell surface expression of NMDA receptor subunits GRIN1 and GRIN2A [UniProt]. LRFN2 interacts with PSD-95 and sorting nexin-27 to regulate AMPA receptor trafficking and synaptic plasticity 2. In the retina, LRFN2 stabilizes cone pedicle contacts with OFF bipolar cells and organizes glutamate receptor clusters to establish visual pathway organization 3. Beyond neurobiology, LRFN2 exhibits tissue-specific expression in pancreatic β-cells 4 and functions as an immunosuppressive factor in bladder cancer, where tumor-intrinsic LRFN2 inhibits CD8+ T-cell recruitment and infiltration, promoting immunotherapy resistance 5. In esophageal squamous cell carcinoma, LRFN2 acts as a tumor suppressor through NMDAR-dependent inhibition of Wnt/β-catenin and NF-κB signaling 6. Loss-of-function LRFN2 mutations are associated with autism-like behaviors and learning disabilities 1, while genetic variants show associations with esophageal cancer susceptibility 7. These findings establish LRFN2 as a multifunctional protein integrating synaptic organization, visual processing, and immune regulation.