Adhesion G protein-coupled receptor L1 (ADGRL1)

Adhesion G protein-coupled receptor L1 (ADGRL1), also known as Latrophilin-1, is a member of the adhesion G protein-coupled receptor (aGPCR) family characterized by an extended extracellular region containing multiple protein domains, including lectin and olfactomedin domains, fused to a 7-transmembrane domain typical of GPCRs via a GAIN autoproteolysis domain[2][1]. ADGRL1 plays key roles in cell adhesion, synaptic development, and signal transduction in the nervous system[1][5][2]. It serves as a high-affinity receptor for the neurotoxin alpha-latrotoxin from black widow spider venom, which can induce massive neurotransmitter release[3][4]. Physiologically, ADGRL1 regulates synapse formation, neuronal signaling, and energy and glucose balance, and interacts with several ligands including teneurins, neurexins, and FLRT proteins[1][4][2]. Mutations in ADGRL1 are linked to neurodevelopmental and neuropsychiatric disorders, including intellectual disability, autism spectrum disorder, ADHD, epilepsy, and also contribute to obesity and cancer risk[1][7][5][3]. ADGRL1 is considered a prototypical adhesive GPCR important for brain function; however, as of current knowledge, it is not directly targeted by any approved pharmacological agents.

Other names

Latrophilin-1LPHN1CIRL1CIRL-1LEC2KIAA0821Calcium-independent alpha-latrotoxin receptor 1Lectomedin-2DEDBANP

Alpha-latrotoxin binds and activates ADGRL1, inducing massive exocytosis of neurotransmitters[3][4]. Endogenous peptide agonists activate G-protein signaling downstream[5]. General GPCR mechanism: Activation leads to intracellular G-protein signal transduction cascade[5][4].