GPR26, also known as G protein-coupled receptor 26, is part of the extensive G protein-coupled receptor (GPCR) superfamily, characterized by seven transmembrane domains¹. These receptors primarily mediate cellular responses to various extracellular signals, such as hormones and neurotransmitters, by coupling with intracellular G proteins, leading to signal transduction cascades^1,3.

GPR26 exhibits high basal activity, stimulating cyclic AMP (cAMP) production in an agonist-independent manner³. It is predominantly expressed in the central nervous system, particularly in the hypothalamus, amygdala, cortex, and striatum^3,5. Cellularly, it localizes to neurons and is involved in central nervous system processes^2,4. Functionally, GPR26 modulates energy balance via hypothalamic AMPK signaling and influences mood regulation by phosphorylating CREB in the amygdala^2,5.

Inactivation of GPR26 in animal models demonstrates its role in obesity, anxiety, and depression. In vitro, its loss enhances hypothalamic activity, causing hyperphagia and metabolic dysregulation, while in vivo, it leads to reduced phosphorylated CREB levels, contributing to anxiety and depression-like behaviors^2,5.

Aberrant GPR26 function is implicated in glioblastomas due to epigenetic silencing, linking it to tumorigenesis¹. It is also associated with neurodegenerative diseases, where it participates in intranuclear inclusion formation in neurons and glial cells⁴.

Research on GPR26 benefits areas like neuropsychiatric disorders, metabolic diseases, cancer, and neurodegeneration, where its detection and functional studies may inform therapeutic developments^1,3.