Other G protein-coupled receptors (GPCRs)

Other G protein-coupled receptors (GPCRs) is a broad classification used to group receptors that do not belong to the major, well-defined subfamilies like rhodopsin-like (Class A), secretin-like (Class B), or glutamate-like (Class C) receptors. This category often includes 'orphan' receptors for which the endogenous ligands remain unidentified, as well as newly discovered receptors with unique structural or functional characteristics (Insel et al., 2019). GPCRs represent the largest family of cell-surface receptors and are responsible for transducing extracellular signals into intracellular responses via G proteins (Hilger et al., 2018). This heterogeneous group is involved in a wide array of biological functions, including signal transduction, sensory perception, and immune response (Santos et al., 2017). Because GPCRs are the targets of approximately 34% of all FDA-approved drugs, this 'other' category represents a significant frontier for drug discovery and therapeutic expansion (Hauser et al., 2017). Dysregulation of various receptors within this group is linked to numerous pathologies, including cancer, metabolic disorders, and central nervous system diseases (Sriram & Insel, 2018). Research into these targets often focuses on de-orphanization and the development of highly selective ligands to minimize off-target effects (Wacker et al., 2017). Therapeutic strategies include the use of small molecule agonists, antagonists, or allosteric modulators to influence specific signaling pathways. The lack of structural data for many members of this group remains a primary challenge in rational drug design. Overall, 'Other GPCRs' serves as a placeholder for a diverse set of potential therapeutic targets that require further characterization.

Other names

Miscellaneous G protein-coupled receptorsOrphan GPCRsNon-classified GPCRsClass Z GPCRs

Agonism, antagonism, or allosteric modulation of specific G protein-coupled receptors within this heterogeneous group (Hauser et al., 2017).