FLRT3 (fibronectin leucine rich transmembrane protein 3) is a transmembrane adhesion molecule with critical roles in neural development, synaptic organization, and immune regulation. Functionally, FLRT3 mediates cell-cell adhesion through interactions with latrophilin GPCRs (ADGRL3, latrophilin-2/3) and promotes neurite outgrowth and synapse formation 1. The protein also functions in axon guidance via interactions with ROBO1 (attraction toward netrin-1) and UNC5B (repulsive signaling) 2. During embryogenesis, FLRT3 is essential for ventral closure, headfold fusion, and endoderm migration 3. In disease contexts, mutations in FLRT3 cause congenital hypogonadotropic hypogonadism (CHH), likely through disruption of fibroblast growth factor pathway signaling 2. Recent evidence implicates FLRT3 in multiple sclerosis pathogenesis, with genetic associations pointing to node of Ranvier and dorsal root ganglion involvement 4. In cancer biology, FLRT3 acts as a coinhibitory ligand for T cells through UNC5B receptor engagement, promoting tumor immune evasion; blocking this pathway with monoclonal antibodies enhances CAR-T cell efficacy 5. Additionally, FLRT3 expression associates with lung cancer risk 6, and SARS-CoV-2 induces FLRT3 upregulation at synapses in infected neural tissue 7. These findings suggest FLRT3 as a multifunctional protein bridging developmental neurobiology with immune and cancer biology.