Rbp4, or retinol-binding protein 4, is a member of the lipocalin family and serves as a specific carrier protein that delivers retinol (vitamin A) from the liver to peripheral tissues. It is predominantly secreted in the liver and adipose tissues. Rbp4 has been implicated in various biological processes and diseases, and is considered an adipokine, a factor secreted by adipose tissue with biological activity [2].

In cardiometabolic diseases (CMD), elevation in serum levels of RBP4, often observed in obese experimental animals and human subjects, is associated with CMD manifestations such as obesity, insulin resistance, and hyperlipidemia [1]. In hyperuricemia-induced rats, RBP4 may be involved in insulin resistance (IR) by inhibiting the phosphorylation of the IRS/PI3K/Akt signaling pathway [5]. In type 2 diabetes patients with kidney diseases, RBP4 concentrations are significantly higher in those with micro-or macro-albuminuria compared to those with normal albuminuria, and are positively correlated with the albumin-to-creatinine ratio (ACR) but negatively correlated with the estimated glomerular filtration rate (eGFR), suggesting it could be a biomarker for kidney diseases in type 2 diabetes [4]. In gestational diabetes mellitus (GDM), circulating RBP4 levels are consistently higher in GDM cases compared to non-GDM controls, indicating its potential as a biomarker for GDM [3].

In conclusion, Rbp4 plays a significant role in multiple disease areas, especially in cardiometabolic-related conditions such as obesity, insulin resistance, and diabetes-associated complications. Its function in these diseases, as revealed through various in vivo studies in animal models and human subjects, provides important insights into the pathophysiological mechanisms, and may potentially lead to new therapeutic approaches targeting Rbp4 for the management of these diseases.