BACKGROUND: The phospholipid-modifying enzyme MBOAT2 plays a crucial role in iron homeostasis by inhibiting iron sequestration, thus preventing iron-induced cell death. It achieves this by remodeling the phospholipid composition of cell membranes through phospholipid metabolism. Although multiple studies have highlighted the significance of MBOAT2 in tumorigenesis, a comprehensive pan-cancer analysis has not been conducted to date. METHODS: In this study, we analyzed the expression levels of MBOAT2 using RNA sequencing data from the TCGA and GTEx databases. We also investigated MBOAT2 protein information using resources such as the Human Protein Atlas (HPA), GeneCards, and String databases. To assess the prognostic value of MBOAT2, we conducted survival analysis based on clinical data from TCGA. Additionally, we performed enrichment analysis using the R package "clusterProfiler" and explored the relationship between MBOAT2 expression and immune cell infiltration, as well as immune checkpoint interactions in TCGA datasets. Furthermore, we examined the correlation between MBOAT2 expression and clinical pathology through immunohistochemical analysis of breast, prostate, lung, and liver cancer tissues in the HPA database. Finally, western blotting was used to validate MBOAT2 protein expression in breast and prostate cancer cell lines. RESULTS: Our analysis revealed that MBOAT2 was highly expressed in a wide range of cancer types, with its expression correlating with improved survival outcomes in the TCGA dataset. Moreover, we found a significant association between MBOAT2 expression and immune regulation, particularly in relation to immune cell infiltration and immune checkpoint interactions. CONCLUSION: MBOAT2 holds promise as a prognostic biomarker and may serve as a target for immunotherapy in various malignancies. Further investigation into its role in cancer immunity could offer new insights into potential therapeutic strategies.