CPLX1 (complexin 1) is a synaptic protein that regulates a late step in exocytosis by organizing SNAREs into a cross-linked zigzag topology that prevents premature neurotransmitter release until action potentials arrive 1. It is also involved in glucose-induced insulin secretion by pancreatic beta-cells and is essential for motor behavior 1. CPLX1 regulates neurotransmitter release and is implicated in dopaminergic and GABAergic neuron function 2. Pathogenic variants in CPLX1 cause developmental and epileptic encephalopathy 63, characterized by severe infantile myoclonic epilepsy, intellectual disability, and developmental delay 3. Homozygous loss-of-function mutations have been identified in families with neurogenetic disorders including brain malformations 4. A case report documented Dravet syndrome with a homozygous CPLX1 mutation and heterozygous SCN9A mutation 5. Beyond neurological disease, CPLX1 has emerged as a prognostic biomarker in gastrointestinal cancers. Elevated CPLX1 expression promotes proliferation, motility, and invasiveness in gastric cancer while decreasing apoptosis and chemotherapy sensitivity 6. Similarly, high CPLX1 expression in colorectal cancer correlates with poor survival outcomes and associates with immunotherapy resistance and ferroptosis dysregulation 78. Additionally, CPLX1 variants near disease-associated loci contribute to vasculitis susceptibility 9.