Purpose of Review <p>Glaucoma is a major cause of irreversible blindness, affecting 295 million individuals and leaving 43 million blind worldwide. With more than 90% of sufferers untreated and up to 20% of treated patients becoming blind within a year, there is a pressing need for new therapeutic strategies. This review aims to explore the potential of MAP4K4 as a novel therapeutic target, addressing its role in glaucoma pathology, including oxidative stress and retinal ganglion cell damage.</p> Recent Findings <p>An extensive literature review was conducted across PubMed and Google Scholar databases (2000–2024), focusing on keywords such as ‘glaucoma’, ‘oxidative stress’, ‘intraocular pressure’, ‘aqueous humor’, and ‘MAP4K4’. Key findings reveal that MAP4K4, a member of the STE20 kinase family, is critically involved in pathways regulating retinal ganglion cell apoptosis, oxidative stress, and trabecular meshwork function. Its inhibition shows promise as a means to alleviate oxidative damage and intraocular pressure, addressing limitations and side effects of current therapies.</p> Summary <p>MAP4K4 is a pivotal regulator in glaucoma-related cellular signaling pathways. This review underscores its therapeutic potential, suggesting that novel MAP4K4 inhibitors could offer effective treatment with minimal side effects, thus enhancing glaucoma management and vision preservation.</p> Graphical Abstract <p></p>