Gpr50, an orphan G protein-coupled receptor highly homologous to melatonin receptors, is located on the X chromosome. It is involved in multiple biological processes, with its functions including the regulation of mitochondrial quality and quantity through mitophagy, participation in TGFβ signaling, and potential associations with synaptic plasticity and cognitive function. It also plays roles in endocrine and metabolic processes, and is linked to the regulation of oocyte maturation, among others [1,2,3,4,5].

In Gpr50-deficient mice, there is an accumulation of damaged mitochondria, disruption of oxidative phosphorylation (OXPHOS), leading to insufficient ATP production, excessive ROS generation, and ultimately impaired neuronal development. These mice also exhibit impaired social recognition, which can be rescued by prenatal treatment with mitoQ, indicating Gpr50's crucial role in maintaining mitochondrial OXPHOS in developing neurons [1]. In neural progenitor cells and tanycytes, Gpr50 knockout increases neurite outgrowth, cell motility and migration, suggesting that Gpr50 acts as an inhibitor of these processes via the G12/13 protein-RhoA pathway [6].

In conclusion, Gpr50 is essential for multiple biological functions, especially in neuronal development and mitochondrial function. The use of Gpr50 knockout mouse models has significantly contributed to understanding its role in neurological processes, highlighting its potential as a target for treating related disorders such as those involving impaired social recognition and abnormal neurite outgrowth.