Human Apolipoprotein L (APOL1) Protein

Background

Apolipoprotein L1 (APOL1) is a member of the Apolipoprotein L gene family and plays a critical role in lipid transport and innate immunity. APOL1 is primarily expressed in the liver, kidney, and vascular endothelium and is known for its ability to bind high-density lipoprotein (HDL) particles, contributing to lipid transport and cholesterol metabolism. A particularly vital function of APOL1 lies in its role in innate immunity, as it helps protect against trypanosome infections. APOL1 can lyse trypanosomes such as Trypanosoma brucei, which cause African sleeping sickness, by disrupting their cellular membranes. Genetic variations, specifically the G1 and G2 risk alleles, have been associated with increased susceptibility to kidney diseases, such as focal segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy (HIVAN), particularly in people of African descent. These alleles enhance APOL1-mediated trypanosome resistance but lead to cytotoxic effects in kidney cells under specific stress conditions. APOL1’s dual role as both a defender against pathogens and a contributor to renal disease makes it a subject of intensive research. Targeting APOL1 signaling pathways may provide therapeutic options for managing kidney diseases and understanding its broader impact on lipid metabolism and immune responses.