B4galt1, also known as beta-1,4-galactosyltransferase1, is a key gene involved in N-glycan biosynthesis [1]. N-glycan biosynthesis pathways play a crucial role in various biological processes, such as cell-cell recognition, immune response, and protein folding and stability.

In lung adenocarcinoma, B4galt1 is highly expressed in invasive adenocarcinoma samples. Function and mechanism experiments in vitro and in vivo showed that it regulates cell proliferation, invasion, and is related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, it directly mediates the N-linked glycosylation of PD-L1 protein, preventing its degradation at the post-transcriptional level and stabilizes the TAZ protein via glycosylation, activating CD274 at the transcriptional level, leading to immune escape. Inhibition of B4galt1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo [1].

In hepatocellular carcinoma, decreased B4galt1 promotes cell invasiveness by regulating the laminin-integrin pathway. Silencing or loss of B4galt1 enhanced cell migration and invasion in vitro and promoted lung metastasis in NOD/SCID mice. It was found that integrins α6 and β1 are the main protein substrates of B4galt1 and their N-glycans are modified by B4galt1 [2].

In conclusion, B4galt1 is important in N-glycan biosynthesis and plays significant roles in multiple diseases. In lung adenocarcinoma, it promotes immune escape, while in hepatocellular carcinoma, its down-regulation promotes cell invasiveness. Studies on B4galt1 using in vitro and in vivo models have provided insights into its functions in disease-related biological processes, which may help develop novel therapeutic strategies for these diseases.