RLN2

RLN2 Full Name

relaxin 2

RLN2 Introduction

RLN2 (relaxin 2) is an important peptide hormone belonging to the relaxin-insulin superfamily and is best known as the major circulating form of human relaxin. Although originally studied in reproductive biology, RLN2 has now emerged as a multifunctional signaling molecule with broad relevance in cardiovascular disease, fibrosis, inflammation, cancer biology, and tissue remodeling. RLN2 primarily exerts its biological effects through the G protein-coupled receptor RXFP1, activating downstream pathways involved in cyclic AMP production, nitric oxide signaling, angiogenesis, extracellular matrix turnover, and cellular migration. Researchers and drug developers are increasingly interested in RLN2 because abnormal tissue fibrosis, vascular dysfunction, and chronic inflammation remain major therapeutic challenges in diseases where current treatments often fail to reverse organ damage. The expanding understanding of the RLN2/RXFP1 signaling axis has therefore positioned this pathway as a promising therapeutic target in regenerative medicine and precision drug discovery.

One of the most clinically significant functions of RLN2 is its ability to regulate collagen remodeling and maintain tissue elasticity. RLN2 promotes matrix metalloproteinase activity while suppressing excessive collagen deposition, making it highly relevant in fibrotic disorders affecting the heart, lungs, liver, and kidneys. In cardiovascular research, RLN2 has attracted substantial attention for its vasodilatory, anti-inflammatory, and anti-fibrotic properties. Studies have shown that RLN2 signaling may improve cardiac output, reduce vascular resistance, and protect against pathological remodeling during heart failure and pulmonary hypertension. Recent investigations into long-acting relaxin analogues, including engineered peptide variants with improved pharmacokinetic stability, have further accelerated interest in RLN2-targeted therapeutics for cardiology applications. Beyond cardiovascular physiology, RLN2 also contributes to embryo implantation, endometrial vascularization, renal hemodynamics, and reproductive tissue adaptation during pregnancy, highlighting its systemic biological importance across multiple organ systems.

Increasing evidence also links RLN2 signaling to cancer progression and tumor microenvironment regulation, although its role appears highly context-dependent. RLN2 and RXFP1 expression have been reported in several malignancies, where the pathway may influence extracellular matrix remodeling, tumor invasion, angiogenesis, macrophage polarization, and metastatic behavior. This dual role creates both opportunities and challenges for therapeutic development, since RLN2 signaling may either suppress fibrosis and improve tissue repair or facilitate tumor cell dissemination depending on cancer type and disease stage. Researchers are therefore actively exploring RLN2 as both a biomarker candidate and a potential therapeutic modulation target in oncology. In colorectal cancer and other solid tumors, RLN2 continues to be evaluated alongside inflammatory and stromal biomarkers to better understand tumor biology and disease progression. As precision medicine increasingly focuses on microenvironment-driven therapies, the RLN2/RXFP1 pathway is becoming a growing area of interest for translational research, peptide engineering, and next-generation anti-fibrotic drug development.

Alternate Names for RLN2

RLN2; relaxin 2; H2; RLXH2; bA12D24.1.1; bA12D24.1.2; relaxin 2 (H2); prorelaxin H2; relaxin H2; relaxin, ovarian, of pregnancy; Relaxin B chain; Relaxin A chain; OTTHUMP00000021027; OTTHUMP00000196912

• 1.Chen TY, et al.; The relaxin family peptide receptor 1 (RXFP1): An emerging player in human health and disease. Mol Genet Genomic Med. 2020, 8(4):e1194.
  2.Wołowiec Ł, et al.; Long-acting relaxin analogues: a novel tool in cardiology. Front Pharmacol. 2025, 16:1626469.