Chemerin Normal Function and Roles in Metabolic and Nonmetabolic Disorders: An Up-To-Date Comprehensive Review

Chemerin (retinoic acid receptor responder 2; RARRES2) is a secreted chemoattractant/adipokine that is expressed mainly in white adipose tissue, liver, and placenta and becomes bioactive after C-terminal proteolytic processing into isoforms with distinct activities. This review summarizes (i) chemerin biosynthesis, processing, receptors, and signaling (CMKLR1/ChemR23, GPR1, and CCRL2), (ii) key physiological roles in immune cell trafficking, adipogenesis, glucose and lipid homeostasis, and vascular biology, and (iii) current evidence linking chemerin signaling to major metabolic disorders and selected nonmetabolic diseases. Overall, circulating chemerin is frequently elevated in obesity, insulin resistance, metabolic syndrome, Type 2 diabetes, nonalcoholic fatty liver disease, and hypertension and often correlates with inflammatory markers; however, heterogeneity in study design, confounding, and limited isoform-specific measurements complicate causal inference and diagnostic validation. Beyond metabolism, chemerin signaling has been implicated in inflammatory conditions (e.g., rheumatoid arthritis and psoriasis) and multiple cancers with tumor type-specific pro- or antitumor effects. Standardized assays, isoform-resolved measurements, and prospective studies are needed to clarify disease mechanisms and determine the clinical utility of chemerin as a biomarker or target.