Relaxin family peptide receptor 4 (RXFP4)

Relaxin family peptide receptor 4 (RXFP4) is a G protein-coupled receptor predominantly activated by its endogenous ligand insulin-like peptide 5 (INSL5). RXFP4 is expressed in tissues such as the colon, kidney, heart, liver, testes, ovary, and distinct regions in the hypothalamus. Activation of RXFP4 by INSL5 or, with lower selectivity, relaxin-3 triggers signaling via Gαi/o proteins, leading to inhibition of cAMP production and activation of downstream kinases such as ERK1/2, Akt, p38MAPK, and S6RP[5][4]. RXFP4 regulates feeding behavior, appetite, energy homeostasis, and colon motility, and has been implicated in metabolic conditions including obesity and diabetes as well as in neuronal control of food preference[5][7]. This receptor is considered a potential therapeutic target for disorders of metabolism and appetite. No specific RXFP4-targeting drugs are currently available, but peptide-based modulators are under research for conditions such as obesity and glucose metabolism disorders[5][1][7].

Other names

G protein-coupled receptor 142 (GPCR142)LGR8-like receptor

Gαi/o protein-coupled signaling: Inhibition of adenylyl cyclase, leading to reduced cAMP; Activation of ERK1/2, Akt, p38MAPK, S6 ribosomal protein upon ligand binding