High density lipoprotein-binding protein (HDLBP)

High density lipoprotein-binding protein (HDLBP), also known as vigilin, is a large, evolutionarily conserved RNA-binding protein characterized by 14 or 15 KH (K-homology) domains[1][2]. It is present at the endoplasmic reticulum membrane, as well as in the cytosol and nucleus, and binds a wide range of RNA species including mRNA, rRNA, and tRNA[1][2]. HDLBP is involved in post-transcriptional regulation, especially in translation of ER-targeted and secreted proteins, cholesterol and lipid transport, and gene expression related to cell sterol metabolism[1][2][4][5]. It has been implicated in the regulation of apolipoprotein synthesis (notably ApoB and ApoC-III), impacting very-low-density lipoprotein (VLDL) secretion, plasma triglyceride, and cholesterol levels, as well as in carcinogenesis, with documented roles in hepatocellular carcinoma and other cancer types[1][2][3]. HDLBP is being studied as both a therapeutic target and a biomarker, with further investigation required to understand its utility in cardiovascular disease and cancer[1][2]. Key recent studies highlight that HDLBP directly interacts with more than 80% of ER-localized mRNAs, regulates their translation, and impacts protein synthesis and secretion, as well as tumor growth in model systems[2]. No direct drugs currently target HDLBP, but cholesterol-lowering agents such as simvastatin can modulate its expression and downstream effects[1].

Other names

VigilinHBPVGLPRO2900HDL-binding proteinHigh density lipoprotein binding protein

Drugs such as simvastatin indirectly affect HDLBP by inhibiting cholesterol synthesis, which modulates HDLBP expression and related cellular phenotypes. No approved direct HDLBP inhibitors or modulators are currently described in the literature.