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While indispensable for neuronal integrity, its role in red blood cells (RBCs) and transfusion outcomes is incompletely understood. Here, we show that novel erythroid\u2010specific\n                    <jats:italic>Pcmt1<\/jats:italic>\n                    knockout mice display profound remodeling of one\u2010carbon metabolism, accumulation of repair intermediates, and destabilization of glycolytic and cytoskeletal proteins, yet maintain lower lipid peroxidation and normal post\u2010transfusion recovery. Analysis of 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study (REDS)\u2010III Red Blood Cell Omics (RBC Omics) study revealed that common\n                    <jats:italic>PCMT1<\/jats:italic>\n                    variants associate with hemolysis phenotypes and regulate PIMT protein level, as gleaned by protein quantitative trait loci (pQTL) analyses. The nonsynonymous rs4816 (V120I) allele, enriched in donors of Asian or African ancestry, emerged as a beneficial variant: carriers exhibited lower osmotic hemolysis, altered peptide methylation flux, and higher PIMT protein levels. Recombinant expression confirmed that the I120 variant displays preserved global folding, but greater catalytic activity than the canonical V120 enzyme. Transfusion outcome data showed that\n                    <jats:italic>PCMT1<\/jats:italic>\n                    genotype influences hemoglobin increments and bilirubin responses in recipients. These findings identify PIMT as a novel determinant of RBC storage biology and establish rs4816 as a protective allele, with broader implications for donor diversity, transfusion efficacy, and proteome maintenance in aging.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70361","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:18:50Z","timestamp":1776338330000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improved red blood cell storage quality of blood from donors carrying the hypermorphic PIMT I120 variant"],"prefix":"10.1002","volume":"10","author":[{"given":"Shaun","family":"Bevers","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron 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Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary B.","family":"Haiman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Nemkov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"},{"name":"Omix Technologies Inc Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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