Sorting (Nexin-13) out Novel Insights into Endolysosomal Cholesterol Export

Abstract

Transport in and out of the endolysosomal compartment represents a key step in the regulation of cellular cholesterol homeostasis. Despite important recent advances, how LDL-derived, free cholesterol is exported from the lumen of endolysosomes to other organelles is still a matter of debate. We recently devised a CRISPR/Cas9 genome-scale strategy to uncover genes involved in the regulation of endolysosomal cholesterol homeostasis and the functionally linked phospholipid, bis(monoacylglycerol)-phosphate. This approach confirmed known genes and pathways involved in this process, and more importantly revealed previously unrecognized roles for new players, such as Sorting Nexin-13 (SNX13). Here we discuss the unexpected regulatory role of SNX13 in endolysosomal cholesterol export.