GPR148 is an orphan G protein-coupled receptor located on chromosome 2.1 that belongs to the Rhodopsin family of Class A GPCRs. Phylogenetic analysis suggests GPR148 may bind prostanoids based on sequence-structure relationships with other characterized receptors 1. The receptor lacks close evolutionary relatives among known GPCRs and appears to be evolving rapidly compared to other orphan receptors in its family 2. GPR148 is expressed primarily in the brain and testes 3. Clinically, GPR148 has been implicated in neurodevelopmental disorders through its location within a recurrent 2q21.1 microdeletion (~450 kb) associated with developmental delay, intellectual disability, attention-deficit hyperactivity disorder (ADHD), epilepsy, and aggressive behavior 3, 4. The deletion occurs through non-allelic homologous recombination between flanking low-copy repeats and affects a five-gene cluster including GPR148 3. Additionally, GPR148 was identified as differentially expressed in type 2 diabetes patients with tuberculosis susceptibility, suggesting potential involvement in immunometabolic pathways 5. Despite functional predictions, GPR148 remains an orphan receptor requiring further characterization to elucidate its endogenous ligands and cellular mechanisms.