NLGN1 (neuroligin 1) is a postsynaptic cell adhesion molecule that mediates cell-cell interactions through neurexin binding, playing a critical role in synaptic function and development 1. At excitatory synapses, NLGN1 recruits and clusters synaptic proteins, promotes presynaptic structure formation, and regulates NMDA and AMPA glutamate receptor clustering 2. Its synaptic localization is dynamically regulated through PKA-dependent phosphorylation of serine 839, which modulates PSD-95 binding and controls surface expression and synaptic enhancement 2. In the prefrontal cortex, NLGN1 expression shifts in response to experience regulate memory consolidation and strengthening through modulation of excitatory-inhibitory balance 1. Genetically, NLGN1 variants associate with multiple neuropsychiatric disorders. Genome-wide analyses identified NLGN1 as a risk locus for suicide attempt across multiple ancestry populations 3, and gene-based testing revealed association with post-traumatic stress disorder, with SNP rs6779753 correlating with increased amygdala activation to fearful faces 4. NLGN1 mutations cause autism spectrum disorder 5. Beyond neurology, elevated NLGN1 expression predicts poor survival in colorectal cancer 6, and single-cell profiling identifies NLGN1-neurexin3 signaling in retinal Müller cells relevant to diabetic retinopathy pathogenesis 7. These findings establish NLGN1 as a multifunctional synaptic protein with broad implications for neuropsychiatric and neoplastic disease.