Gpr25, an orphan G protein-coupled receptor, has been implicated in various physiological and pathological processes. It may be associated with autoimmune diseases and blood pressure regulation in humans [3]. Gpr25 has shown constitutive activity within the cAMP signaling pathway, where it inhibits both baseline and forskolin-stimulated expression, suggesting its role in cAMP-mediated signaling regulation [2].

In mouse models, Gpr25 is characterized as a lymphocyte receptor for CXCL17. This GPR25-CXCL17 chemoaffinity axis mediates lymphocyte homing to barrier epithelia of non-intestinal mucosal tissues such as airways, oral cavity, stomach, and biliary and genitourinary tracts. It also plays a role in central nervous system (CNS) immune regulation as Gpr25 is expressed by T cells in cerebrospinal fluid and CXCL17 by neurons. Additionally, widespread imprinting of Gpr25 on regulatory T cells may link it to protection in autoimmunity based on population genetics evidence [1].

In conclusion, Gpr25 is crucial in immune-related processes, especially in the homing of lymphocytes to non-intestinal mucosal tissues and CNS immune regulation. Mouse models have been instrumental in revealing these functions, providing insights into its potential role in autoimmune diseases. The identification of Gpr25 as a receptor for CXCL17 further paves the way for understanding its functions in immune-mediated diseases [1,4].