The role of the Niemann–Pick C1-like 1 protein in the subcellular transport of multiple lipids and their homeostasis

Abstract

In the past 2 years the Niemann-Pick C1-like 1 protein has rapidly emerged as a key regulator of intestinal cholesterol absorption. This review covers the limited number of published reports to develop a hypothesis of the potential function of Niemann-Pick C1-like 1 protein and outlines questions that should be addressed in future studies. Considerable disagreement regarding the potential function and subcellular location of Niemann-Pick C1-like 1 protein has complicated interpretation of published results and evaluation of their biologic significance. Recent reports suggest, however, that Niemann-Pick C1-like 1 protein plays a key role in modulating the subcellular fate of multiple lipids including cholesterol and sphingolipids. In addition, this function may require Niemann-Pick C1-like 1 protein to move between different cellular locations. This paper proposes a model of Niemann-Pick C1-like 1 protein function based on available data and on knowledge of its close relative and homologue the Niemann-Pick C1 protein, whose precise function, albeit still elusive, is more extensively characterized. It also raises new questions with respect to Niemann-Pick C1-like 1 protein function and discusses potential future directions.