Cholesterol is an essential lipid component of membranes and is a precursor of a wide range of signalling molecules. Disturbed cholesterol homeostasis is predominantly associated with the development of cardiovascular disease, but it is now clear that this also plays a critical role in, amongst others, metabolic-associated fatty liver disease (MASLD) and its transition to hepatocellular carcinoma, malignancies broadly, and neurodegenerative disease (e.g. Alzheimer’s Disease, AD). In cells, cholesterol is unevenly distributed between organelle membranes to maintain cellular and organismal cholesterol homeostasis. The lysosome is an essential cholesterol-trafficking hub, as is clearly illustrated in lysosomal cholesterol diseases such as Niemann-Pick disease (NPC) and lysosomal lipase deficiency diseases. Cholesterol egress from lysosomes involves membrane contact sites (MCS) and several proteins that have been recently identified. Interestingly, studies have shown that these MCS and subcellular localization of lysosomes are critically controlled by intracellular levels and distribution of cholesterol itself. In this project, we aim to answer how lysosomal cholesterol egress, and the intracellular cholesterol state are molecularly intertwined to maintain cellular and organismal cholesterol homeostasis. This position offers a unique opportunity to work at the forefront of organelle biology, cholesterol metabolism, physiology, and proteomics analyses, with access to cutting-edge molecular tools and a collaborative research environment.