CPLX3 (complexin 3) is a synaptic protein located on chromosome 15 that regulates SNARE-mediated synaptic vesicle fusion and neurotransmitter release. In the retina, CPLX3 maintains synaptic ultrastructure and positively regulates synaptic transmission at photoreceptor ribbon synapses by modulating synaptic vesicle availability and exocytosis 1. CPLX3 functions to suppress tonic photoreceptor activity and baseline noise through suppression of spontaneous Ca2+ vesicle release while facilitating evoked synchronous and asynchronous release. During cortical development, CPLX3 is expressed as a layer 6b-specific gene whose expression is regulated by transcription factors Satb2 and Nr4a2, marking mature subplate neurons that regulate cortical development and plasticity 23. CPLX3 is clinically relevant in 15q24 microdeletion syndrome, where its deletion along with SEMA7A and SIN3A contributes to developmental delay and intellectual disability 45. Additionally, CPLX3 downregulation correlates with poor overall survival in glioblastoma 6, and its methylation status shows ancestry-specific associations with daytime sleepiness in African-Americans 7. CPLX3 has also been identified as a hub gene in atrial fibrillation associated with primary mitral regurgitation 8.