B4galnt4, also known as β-1,4-N-Acetyl-galactosaminyltransferase 4, is an enzyme involved in ganglioside synthesis and in the synthesis of GalNAcβ1-4GlcNAc (LacdiNAc or LDN), a subterminal glycan structure. This LDN structure is involved in the clearance of N-glycoproteins from the blood and maintenance of cell stemness [2].

In esophageal squamous cell carcinoma (ESCC), knockdown of B4GALNT4 significantly suppressed the proliferation, invasion, migration, and adhesion of ESCC cell lines. High B4GALNT4 mRNA and protein expression were significantly associated with poor disease-free survival, hematogenous recurrence, and poor disease-specific survival, making it an independent predictor of poor prognosis for ESCC patients [1]. In prostate cancer, studies have identified B4GALNT4 as part of a prognostic signature related to cuproptosis, androgen biosynthetic and catabolic pathways, and in the TMPRSS2-ERG molecular subtype, suggesting its potential role in prostate cancer progression [3,4,5].

In conclusion, B4galnt4 is an enzyme crucial for specific glycan synthesis with implications in maintaining normal biological functions related to glycoprotein clearance and cell stemness. Its role in cancer, particularly in ESCC and prostate cancer, as indicated by knockdown studies, shows its potential as a prognostic marker and a possible therapeutic target, highlighting the importance of research on B4galnt4 for understanding cancer progression and developing new treatment strategies.