ADGRL1, also known as latrophilin 1, is an adhesion G protein-coupled receptor. It is involved in synaptic development, maturation, and activity [1]. It has also been implicated in mediating energy and glucose homeostasis [2]. In the brain, it may play a role in glucose-sensing pathways, and its function is related to the regulation of systemic glucose and energy balance.

In gene knockout studies, Adgrl1-knockout mice on a non-permissive background with a heterozygous null allele showed neurological and developmental abnormalities, while homozygous mice were non-viable [1]. On a permissive background, surviving Adgrl1-/-mice demonstrated stereotypic behaviors, sexual dysfunction, abnormal locomotion, augmented startle reflex, and attenuated pre-pulse inhibition, along with increased spontaneous exocytosis of neurotransmitters and poor in vitro synapse formation [1]. Global and hypothalamus-specific Adgrl1-knockout mice showed fasting hyperinsulinaemia, enhanced glucose-stimulated insulin secretion, insulin resistance, and impaired feeding responses to glucose and fasting [2]. Also, mice lacking Adgrl1 in the ventromedial nucleus of the hypothalamus had abnormal glucose sensing and decreased physical activity before developing obesity and hyperglycaemia [2].

In conclusion, Adgrl1 is crucial for synaptic and metabolic functions. Gene knockout mouse models have revealed its role in neurodevelopmental disorders, energy, and glucose homeostasis. These findings suggest that understanding Adgrl1 function may provide insights into treating related neurological and metabolic diseases.