HDLBP, also known as vigilin, is a member of an evolutionarily conserved family of RNA-binding proteins. It contains 14 or 15 RNA-interacting KH domains and is involved in multiple processes such as translation, chromosome segregation, cholesterol transport, and carcinogenesis [3]. It is mainly present at the cytoplasmic face of the endoplasmic reticulum, as well as in the cytosol and nucleus.

In hepatocellular carcinoma (HCC), HDLBP shows elevated expression. Knockdown of HDLBP inhibits HCC cell proliferation, sorafenib resistance, metastasis, invasion, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. HDLBP stabilizes lncFAL, which in turn reduces ferroptosis vulnerability by abolishing Trim69-dependent FSP1 polyubiquitination degradation [1]. It also stabilizes RAF1 by competing with TRIM71 E3 ligase, promoting HCC progression [2]. In addition, HDLBP interacts with BRAF, inhibits its ubiquitinated degradation, and promotes EMT signaling in a BRAF-dependent manner [4]. In lung adenocarcinoma, HDLBP promotes glycolysis and CD8+ T cell exhaustion by stabilizing GJB2 RNA [5]. In small cell lung cancer, attenuating HDLBP expression with siRNA inhibits cell proliferation, metastasis in vitro and tumor formation in vivo [6].

In conclusion, HDLBP plays crucial roles in multiple biological processes, especially in cancer-related mechanisms. Studies using knockdown (functionally similar to loss-of-function in KO models) in various cancer cell lines and in vivo mouse models have revealed its significance in HCC, lung adenocarcinoma, and small cell lung cancer, suggesting it could be a potential biomarker and therapeutic target for these cancers.