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This review critically evaluates the domain\u2010specific functions of lipin\u20101 and their impact on disease progression. Accumulating evidence indicates that lipin\u20101 exerts divergent, domain\u2010dependent effects. The transcriptional coregulatory activity of lipin\u20101 promotes peroxisome proliferator\u2013activated receptor\/peroxisome proliferator\u2013activated receptor \u03b3 coactivator 1\u2010\u03b1 signaling, enhances fatty acid \u03b2\u2010oxidation and oxidative phosphorylation, and supports interleukin\u20104\u2013driven proresolving macrophage polarization. It also enhances efferocytosis, suppresses sterol regulatory element\u2013binding protein\u2013mediated lipogenesis, and reduces oxidized low\u2010density lipoprotein\u2013induced foam\u2010cell formation. These effects are associated with reduced necrotic core formation, lower interleukin\u201023 signaling, diminished macrophage necroptosis, and improved plaque stability in experimental models. In contrast, the phosphatidic acid phosphatase enzymatic activity of lipin\u20101 activates diacylglycerol\u2010dependent protein kinase C\u2013extracellular signal\u2010regulated kinase\u2013 activator protein\u20101 and toll\u2010like receptor 4 signaling, promotes inflammatory eicosanoid production, enhances oxidized low\u2010density lipoprotein uptake, impairs cholesterol efflux, and accelerates foam\u2010cell formation and vascular inflammation. Myeloid\u2010specific loss of phosphatidic acid phosphatase activity reduces lesion size and inflammatory burden while improving macrophage lipid handling. Collectively, current evidence supports a domain\u2010 and context\u2010dependent role for lipin\u20101 in atherosclerosis. The transcriptional coregulatory function appears predominantly atheroprotective, whereas phosphatidic acid phosphatase enzymatic activity is proinflammatory and atherogenic. Selective modulation of lipin\u20101 activity in macrophages may therefore represent a promising therapeutic strategy to limit atherosclerosis progression while preserving inflammation\u2010resolving pathways.<\/jats:p>","DOI":"10.1161\/jaha.126.050155","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:18:40Z","timestamp":1785496720000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Lipin\u20101 in Macrophage\u2010Mediated Atherosclerosis: Is It Atherogenic or Atheroprotective?"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-0741","authenticated-orcid":false,"given":"Farnaz","family":"Oghbaei","sequence":"first","affiliation":[{"name":"Tabriz Medical Sciences, Islamic Azad University","place":["Tabriz, 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