In this study, we searched the GWAS atherosclerosis database and identified a single nucleotide polymorphism (SNP) located in the intron of LINC00305. Functional analysis and additional mechanistic studies demonstrated that LINC00305 is a novel modulator of NF-κB activity by targeting lipocalin-1 interacting membrane receptor (LIMR) and aryl-hydrocarbon receptor repressor (AHRR), and revealed the role of LINC00305 in promoting monocytes inflammation and phenotypic switching in human aortic smooth muscle cells (HASMCs), critical steps in the pathogenesis of atherosclerosis. Here, NFKB1 is linked to atherosclerosis.