Unc119b is one of the paralogs of the guanine dissociation inhibitor-like solubilizing factors UNC119 in the human genome. It binds to N-myristoylated proteins, facilitating their trafficking between different membranes, and is involved in the shuttling and sorting of lipid-modified proteins to the primary cilium [2,4,5]. It may also play a role in insulin sensitivity as Unc119 proteins were identified as targets of compounds that enhance insulin-stimulated GLUT4 translocation [3].

In hepatocellular carcinoma (HCC), a Cox model including Unc119b suggested unfavorable overall survival in the high-risk score group. Unc119b, along with NR6A1 and OSBP2, could inhibit NK cell and TIL cell infiltration, and impair Type-I and II IFN responses in HCC, contributing to poor prognosis and immunotherapy resistance. Unc119b was also related to chemotherapy resistance [1].

In zebrafish, knockdown of unc119b orthologs led to visual impairment and early-onset retinal dystrophy, indicating its importance in cone function [6]. In cep290-deficient zebrafish, upregulation of unc119b was associated with milder phenotypes, suggesting a role in genetic compensation for cilia defects [7].

Low-dose ionizing radiation led to promoter hypermethylation and transcriptional downregulation of Unc119b in endothelial cells, making it a potential DNA methylation biomarker for cardiovascular risk assessment [8].

In conclusion, Unc119b is crucial for the trafficking of myristoylated proteins, especially in ciliary processes. Its role in diseases such as HCC, as revealed through model-based research, indicates its potential as a therapeutic target. The findings from zebrafish models also highlight its significance in visual function and cilia-related genetic compensation. Additionally, its response to low-dose radiation in endothelial cells shows promise as a biomarker for cardiovascular risk [1,6,7,8].