Regulation of PCSK9 expression. Transcriptional factors, such as SREBP2, HNF-1α, SP-1and E2F2, upregulate PCSK9 transcription. FGF21 and resistin inhibit and increase SREBP2-mediated transcription of PCSK9, respectively. Barberine reduces PCSK9 expression via suppressing the activity of SREBP2 and HNF-1α on PCSK9 transcription. 9K suppresses PCSK9 expression through SP1 and HNF-1α, while Curcumin, 7030B-C5 inhibits HNF-1α-induced transcription of PCSK9. Alcohol use causes hypomethylation of PCSK9 promoter and then reduces PCSK9 expression. Insulin activates mTROC1 and then PKCδ to suppress PCSK9 transcription via HNF-1α. miR-483-5p, miR-1228-3p, miR-143-5p, miR-564, and miR-4721 bind to the 3'UTR of PCSK9 mRNA, reducing PCSK9 expression, while miR27a somehow increases PCSK9 expression. R-IMPP inhibits 80S ribosome and reduces PCSK9 expression. After autocleavage in the ER, PCSK9 is transported to the Golgi via classical COPII vesicles. There, PCSK9 undergoes posttranslational modifications, such as phosphorylation, glycosylation, and sulfation. Mature PCSK9 is then secreted into the extra cellular environment.