FLRT2 (fibronectin leucine rich transmembrane protein 2) is a transmembrane receptor mediating cell-cell adhesion and axon guidance through interactions with adhesion molecules and guidance receptors. The protein functions as a vein-specific regulator of vascular development, interacting with VE-cadherin to modulate adherens junction morphology and regulate blood-brain barrier formation 1. FLRT2 prevents endothelial cell senescence via the ITGB4/mTORC2/p53 signaling pathway, with reduced expression observed in aged vascular tissues; FLRT2 overexpression rescues premature vascular aging in mice 2. Beyond vascular functions, FLRT2 drives monocyte-to-macrophage differentiation through UNC5B-mediated Akt/mTOR pathway activation 3. The protein exhibits tumor-suppressive properties in bladder cancer by elevating ACSL4 expression and facilitating ferroptosis 4. Structurally, FLRT2 forms homodimers in cis via dual Small-X3-Small transmembrane motifs, enabling competitive switching between cis and trans interactions 5. In the central nervous system, FLRT2 haplodeficiency enhances spatial memory and synaptic plasticity in females via estrogen receptor-dependent mechanisms 6. Clinically, lower baseline FLRT2 levels associate with choroid plexus expansion in multiple sclerosis patients, suggesting involvement in neuroinflammatory processes 7. These diverse functions position FLRT2 as a multifunctional regulator relevant to vascular health, immune homeostasis, cancer progression, and neuroinflammation.