ADGRL1 (adhesion G protein-coupled receptor L1) is an adhesion GPCR functioning as a calcium-independent, high-affinity receptor for alpha-latrotoxin and TENM2, mediating synaptic cell-cell contact and postsynaptic specialization 1. The receptor acts as a signaling platform connecting trans-cellular interactions to cellular responses through G protein activation and recruitment of postsynaptic scaffolds, with its function regulated by extensive alternative splicing 2. ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans, including developmental delay, intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy 3. In heterozygous carriers, ADGRL1 variants show faulty ligand-induced calcium signaling, while Adgrl1-knockout mice exhibit stereotypic behaviors, sexual dysfunction, altered locomotion, and increased spontaneous neurotransmitter exocytosis 3. Beyond neuronal function, ADGRL1 serves as a glucose receptor in the hypothalamus, binding glucose to regulate energy and glucose homeostasis in a sex-dependent manner; dysfunction increases obesity risk and impairs glucose sensing 45. ADGRL1 variants associate with developmental epileptic encephalopathy and genetic epilepsy with febrile seizures plus, with variant location predicting severity 6. The protein's upregulation in certain cancers correlates with poor prognosis, suggesting potential as an immunotherapeutic target 78.