Many common diseases have a polygenic architecture. The responsible alleles are thought to mediate risk by disturbing gene regulation in most cases, however, the precise mechanisms have been elucidated only for a few. Here, we investigated the genomic locus, which genome-wide significantly associates with coronary artery disease, a globally leading cause of death caused by accumulation of lipid-rich inflammatory plaques in the arterial wall. The locus harbors whose mRNA and protein we found to be suppressed in atherosclerotic human and mouse arteries. Loss-of-function(LoF) variants of were associated with detrimental cardiovascular phenotypes in the UK Biobank. Its knock-out increased plaque-sizes in / mice compared to mice on a Western diet. After establishing an atheroprotective role of CDH13 we studied its regulation. Integration of population genomic and transcriptomic datasets by GWAS-eQTL colocalization analysis identified and four long non-coding RNAs (lncRNAs) as candidate causal genes at the locus. dCas13-mediated RNA immunoprecipitation revealed that the lncRNA binds to mRNA in human endothelial cells (ECs). Its CRISPR/Cas9-based knockout in ECs was atherogenic, whereas dCas9-based transcriptional activation (CRISPRa) of was atheroprotective; effects that were found to be mediated by the stability of mRNA. To further understand how the protects the mRNA we searched and screened for microRNAs (miRNAs) that bind to 3'UTR. Indeed, four miRNAs, miR-19b-3p, miR-125b-2-3p, miR-433-3p, and miR-7b-5p, were found experimentally to accelerate mRNA degradation, an effect that was neutralized by CRISPRa of . Taken together, our study demonstrates an interplay of miRNAs, lncRNAs, and mRNA, which modulates the abundance of an atheroprotective protein in endothelial cells, which may offer a new therapeutic target for coronary artery disease.