Latrophilin G protein-coupled receptor (Latrophilin (Lphn); for individual isoforms: Latrophilin-1 (Lphn1), Latrophilin-2 (Lphn2), Latrophilin-3 (Lphn3))

Latrophilins are a subset of adhesion G protein–coupled receptors (adhesion-GPCRs), with three main isoforms: Latrophilin-1 (ADGRL1), Latrophilin-2 (ADGRL2), and Latrophilin-3 (ADGRL3)[4][5][8]. **Latrophilins** are membrane receptors characterized by a large N-terminal extracellular region (including lectin and olfactomedin domains) linked through a GAIN domain to a seven-transmembrane GPCR core[4][5][8]. They are best known as the brain receptors for α-latrotoxin (from black widow spider venom), which triggers massive exocytosis at synapses[4][7]. Functionally, latrophilins mediate both cell adhesion and classical GPCR signal transduction, including constitutive and ligand-induced increases in cAMP[1][3][6]. Latrophilin-2 and Latrophilin-3, in particular, are essential for synapse formation and proper connectivity in the hippocampus, acting postsynaptically in trans-synaptic complexes with proteins such as teneurins and FLRTs[1][3][6][9]. Emerging data suggest roles in heart development (Latrophilin-2), cell proliferation, and cancer stem cell function. While not presently targeted by pharmacological drugs, latrophilins are of increasing interest in neuroscience and regenerative medicine due to their specific and essential signaling roles[5][8].

Other names

Adhesion G protein-coupled receptor L1 (ADGRL1, Latrophilin-1)Adhesion G protein-coupled receptor L2 (ADGRL2, Latrophilin-2)Adhesion G protein-coupled receptor L3 (ADGRL3, Latrophilin-3)LPHN1, LPHN2, LPHN3Latrophilin receptor

Agonism by α-latrotoxin triggers exocytosis at neuron synapses (extreme depolarization); Synthetic *Stachel* peptides can activate the receptor via the conserved tethered agonist sequence in the GAIN domain