ORP1L (Oxysterol-binding protein-related protein 1L) is a lipid transfer protein that belongs to the family of OSBP-related proteins (ORPs). It is recruited to lysosomes via its ankyrin repeat domains that bind to Rab7(PMID: 34504082). ORP1L also possesses an FFAT motif, which allows it to interact with the ER resident VAP proteins to aid in establishing the ER-lysosomes contacts. ORP1L is expressed in various tissues, with particularly high expression in the brain, lungs, and macrophages. ORP1L plays a crucial role in cholesterol homeostasis. Disruption of ORP1L function can lead to a block in cholesterol transport to the ER, resulting in the accumulation of cholesterol-enriched LELs in the Golgi/perinuclear region. This can disrupt cellular cholesterol balance, potentially contributing to various metabolic diseases. This suggests that ORP1L is necessary for the normal functioning of cholesterol export from the endo-lysosomal system to the ER, and its dysfunction could be implicated in the progression of diseases related to cholesterol metabolism dysregulation(PMID: 28564600). The molecular weight of ORP1L is 50 kDa.