LRRTM4 is a leucine-rich repeat transmembrane protein that functions as a postsynaptic adhesion molecule critical for excitatory synapse development and maintenance in the nervous system. Mechanistically, LRRTM4 mediates trans-synaptic interactions through heparan sulfate proteoglycan (HSPG) receptors, particularly glypican 1, and engages in a transsynaptic complex with pikachurin at rod photoreceptor synapses 2. LRRTM4 shows cell-type-specific expression in the hippocampus, localizing to excitatory postsynaptic sites on dentate gyrus granule cells where it regulates synapse density and activity-dependent AMPA receptor trafficking 3. Clinically, LRRTM4 variants associate with neuropsychiatric conditions. Sex-specific genetic variations in LRRTM4 link to attempted suicide in bipolar disorder patients, with variants potentially regulating LRRTM4 brain expression and overlapping hormone response elements 4. LRRTM4 duplication appears associated with Tourette syndrome and autism spectrum disorder 5. A novel p.C538Y mutation causes autosomal dominant macular dystrophy with impaired ON-type bipolar cell function 6. Additionally, LRRTM4 expression correlates with cancer-associated fibroblast infiltration in intrahepatic cholangiocarcinoma, serving as a prognostic biomarker 7.