Functional implications of sterol transport by the oxysterol-binding protein gene family

Cholesterol and its numerous oxygenated derivatives (oxysterols) profoundly affect the biophysical properties of membranes, and positively and negatively regulate sterol homoeostasis through interactionwith effector proteins.As the bulk of cellular sterols are segregated from the sensorymachinery that controls homoeostatic responses, an important regulatory step involves sterol transport or signalling between membrane compartments. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, such as the eukaryotic family of OSBP (oxysterol-binding protein)/ORPs (OSBP-related proteins). Since the founding member of this family was identified more than 25 years ago, accumulated evidence has implicated OSBP/ORPs in sterol signalling and/or sterol transport functions. However, recent evidence of sterol transfer activity by OSBP/ORPs suggests that other seemingly disparate functions could be the result of alterations in membrane sterol distribution or ancillary to this primary activity.