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GLS1 (glutaminase 1), a rate\u2010limiting enzyme catalyzing the conversion of glutamine to glutamate, is disordered in various cardiovascular diseases. However, the potential interplay between GLS1\u2010mediated glutamate production and arterial calcification remains poorly understood. Here, LC\u2010MS\/MS analysis of CKD patients\u2019 samples shows an abnormally elevated activity of GLS1, reflected by the increased glutamate\/glutamine ratio. Moreover, GLS1 activity is positively correlated with arterial calcification progression, and its expression is upregulated in calcified arteries. Treatment with GLS1 inhibitors or knockdown of GLS1 alleviates osteogenic reprogramming. In contrast, glutamate administration boosts the development of arterial calcification. Mechanistically, GLS1 redundancy\u2010regulated glutamate superfluity stimulates the activation of N\u2010methyl\u2010d\u2010aspartate receptors (NMDAR), leading to Ca<jats:sup>2+<\/jats:sup> influx and extracellular regulated protein kinases (ERK) phosphorylation, followed by the nuclear translocation of <jats:italic>\u03b2<\/jats:italic>\u2010Catenin and acceleration of osteogenic reprogramming of vascular smooth muscle cells (VSMCs) in further. This research defines GLS1 as a key contributor to arterial calcification. Glutamate, a major product of GLS1\u2010mediated glutamine metabolism, exerts a deleterious effect on arterial calcification by activating NMDAR and subsequently triggering Ca<jats:sup>2+<\/jats:sup> influx, which in turn exacerbates <jats:italic>\u03b2<\/jats:italic>\u2010Catenin\u2010regulated osteogenic reprogramming in VSMCs.<\/jats:p>","DOI":"10.1002\/advs.202414252","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T03:31:55Z","timestamp":1745811115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GLS1\u2010Mediated Redundancy in Glutamate Accelerates Arterial Calcification via Activating NMDAR\/Ca<sup>2+<\/sup>\/<i>\u03b2<\/i>\u2010Catenin Pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Ziting","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology Joint Laboratory of Guangdong\u2010Hong Kong\u2010Macao Universities for 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