LRRTM2 is a postsynaptic cell-adhesion molecule that functions as a key regulator of excitatory glutamatergic synapse development and maintenance 1. Structurally, LRRTM2 contains leucine-rich repeat domains and functions as a ligand for presynaptic neurexins, specifically binding neurexin-1α and neurexin-1β variants lacking a splice site 4 insert in a calcium-dependent manner 2. This binding triggers presynaptic differentiation and instructs the development of functional glutamate release sites at the synapse 1. LRRTM2 cooperates with neuroligin-1 in an additive or synergistic manner to regulate synaptic assembly, and notably exhibits greater potency than neuroligin-1 in promoting synaptic differentiation 3. The gene is nested within the seventh intron of CTNNA1, sharing a bidirectional promoter that regulates alternative transcription of both genes in the nervous system 4. Clinically, microdeletions encompassing LRRTM2 at 5q31.2 have been associated with intellectual disability and developmental delay, identifying LRRTM2 as a candidate gene for neurodevelopmental disorders 5. However, sequencing studies in 330 ID/DD patients revealed no frequent point mutations, suggesting haploinsufficiency rather than loss-of-function mutations drives LRRTM2-related pathology 5.