Polymorphic SLC22A16 and SLC22A5 associate with depletion of AC pools and elevated osmotic hemolysis. End-of-storage REDS RBC Omics index (n = 13 091) and recalled donor samples (n = 643; storage day 10, 23, and 42) underwent metabolomics only, or combined metabolomics, proteomics, lipidomics, and trace element analyses via ICP-MS (A). Correlation of these data sets in index (B-C) and recalled (D-E) sets highlighted a negative association between allele copies for SLC22A16 rs12210538 and SLC22A5 rs272855 and AC pools (x-axis indicate Spearman rho; y-axes indicate −log₁₀(p)). (F-G) Donors who are homozygous recessive for either polymorphism show significantly higher levels of osmotic hemolysis (violin plots show median ± interquartile ranges and distribution of values across the population; each individual dot is a separate sample; asterisks indicate significance: adjusted ∗P < .05 and ∗∗∗∗P < .0001).