RXFP1

RXFP1 (relaxin family peptide receptor 1) is a class A G protein-coupled receptor that mediates signaling by relaxin and functions as a key regulator of tissue remodeling, extracellular matrix turnover, reproductive physiology, and cardiovascular homeostasis^[1][2]. Mechanistically, RXFP1 activation engages intracellular signaling networks including PI3K and NOS-NO-cGMP pathways, which suppress TGF-β1 signaling and contribute to the well-established antifibrotic actions of the relaxin/RXFP1 axis^[3][1]. Consistent with these biological functions, relaxin/RXFP1 signaling has been implicated in fibrosis, cardiovascular disease, and tissue repair, while reduced RXFP1 expression in fibrotic lung and skin tissues is associated with impaired responsiveness to relaxin and disrupted receptor signaling^[1]. In disease models, altered RXFP1 expression, alternative splicing, and receptor dimerization have emerged as important mechanisms regulating receptor activity and may influence pathological progression as well as therapeutic responsiveness^[1]. Compared with the closely related isoform RXFP2, which is selectively activated by insulin-like peptide 3 (INSL3), RXFP1 displays distinct ligand recognition and activation mechanisms despite substantial structural similarity between the two receptors^[4]. RXFP1 contains a characteristic large extracellular domain with leucine-rich repeats and an essential LDLa module that contributes to receptor activation, distinguishing it from many conventional GPCRs^[4][5]. For experimental applications, recombinant relaxin, peptide agonists, and emerging small-molecule RXFP1 agonists have been used to investigate receptor pharmacology and antifibrotic signaling, supporting RXFP1 as a valuable target in cardiovascular and fibrosis-related research^[6][7][8].