ELFN2 is a postsynaptic cell adhesion molecule that plays essential roles in synaptic signaling and neuropsychiatric function through its interaction with group III metabotropic glutamate receptors (mGluRs) 1. The protein contains extracellular leucine-rich repeats and fibronectin type III domains that enable trans-synaptic binding to presynaptic mGluRs, critically altering G protein coupling kinetics and efficacy of these receptors 1. ELFN2 exists as an obligate homodimer and can form heterodimers with its homolog ELFN1, with dimerization occurring through the extracellular leucine-rich repeat domain 2. Loss of ELFN2 in mice results in selective downregulation of group III mGluRs, dysregulated glutamatergic transmission, and neuropsychiatric manifestations including seizure susceptibility, hyperactivity, and anxiety/compulsivity 1. In disease contexts, ELFN2 has been implicated in glioblastoma where it promotes autophagy by interacting with AurkA and eIF2α 3, and its expression is regulated by DNA methylation changes 4. The protein serves as a hub gene targeted by DDX43 during spermiogenesis 5 and is associated with endometrial carcinoma progression through miRNA regulatory networks 6.