FLRT1 is a transmembrane leucine-rich repeat protein that functions as a cell adhesion and signaling molecule with roles in neurodevelopment and potentially in disease pathogenesis. Structurally, FLRT1 contains 10 leucine-rich repeats flanked by cysteine-rich regions, a fibronectin/collagen-like domain, and is glycosylated at the cell surface, localizing to focal adhesion-containing cell-cell contacts 1. FLRT1 regulates fibroblast growth factor (FGF) signaling by interacting with FGFR1 and can be induced by FGF-2 activation 2. The protein forms context-dependent higher-order complexes with latrophilin adhesion-GPCRs and Unc5 guidance receptors, enabling both cell adhesion and repulsion responses 3. Functionally, FLRT1 controls cortical neuronal migration and intercellular adhesion, with FLRT1/3 deletions resulting in cortical folding through altered neuron migration patterns independent of progenitor amplification 4. Disease relevance includes association with pediatric high-grade gliomas through potential enhancer hijacking mechanisms 5 and glioblastoma prognosis, where FLRT1 upregulation associates with longer survival 6. Additionally, rare FLRT1 variants have been identified in a familial schizophrenia cohort, implicating it in neurodevelopmental and neurotransmitter signaling pathways 7, and sex-specific genetic variation at MACROD1/FLRT1 loci influences early-onset periodontitis risk 8.