The Emerging Roles of Intracellular PCSK9 and Their Implications in Endoplasmic Reticulum Stress and Metabolic Diseases
Paul F. Lebeau,
Khrystyna Platko,
Jae Hyun Byun,
Yumna Makda,
Richard C. Austin
Affiliations
Paul F. Lebeau
Department of Medicine, Division of Nephrology, Institute of St. Joe’s Hamilton, The Hamilton Center for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Khrystyna Platko
Department of Medicine, Division of Nephrology, Institute of St. Joe’s Hamilton, The Hamilton Center for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Jae Hyun Byun
Department of Medicine, Division of Nephrology, Institute of St. Joe’s Hamilton, The Hamilton Center for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Yumna Makda
Department of Medicine, Division of Nephrology, Institute of St. Joe’s Hamilton, The Hamilton Center for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Richard C. Austin
Department of Medicine, Division of Nephrology, Institute of St. Joe’s Hamilton, The Hamilton Center for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
The importance of the proprotein convertase subtilisin/kexin type-9 (PCSK9) gene was quickly recognized by the scientific community as the third locus for familial hypercholesterolemia. By promoting the degradation of the low-density lipoprotein receptor (LDLR), secreted PCSK9 protein plays a vital role in the regulation of circulating cholesterol levels and cardiovascular disease risk. For this reason, the majority of published works have focused on the secreted form of PCSK9 since its initial characterization in 2003. In recent years, however, PCSK9 has been shown to play roles in a variety of cellular pathways and disease contexts in LDLR-dependent and -independent manners. This article examines the current body of literature that uncovers the intracellular and LDLR-independent roles of PCSK9 and also explores the many downstream implications in metabolic diseases.
