The evolutionarily conserved VPS13 family proteins have been implicated in several cellular processes. Mutations in each of the four human VPS13s cause neurodevelopmental or neurodegenerative disorders. Until recently, the molecular function of VPS13 remained elusive. Genetic, functional and structural studies have now revealed that VPS13 acts at contact sites between intracellular organelles to transport lipids by a novel mechanism: direct transfer between bilayers via a hydrophobic channel that spans its entire rod-like N-terminal half. Predicted similarities to the autophagy protein ATG2 suggested a similar role for ATG2 that has now been confirmed by structural and functional studies. Here, after a brief review of this evidence, we discuss what is known of human VPS13 proteins in physiology and disease.

进化上保守的 VPS13 家族蛋白与多种细胞过程有关。四种人类 VPS13 中的每一种的突变都会导致神经发育或神经退行性疾病。直到最近，VPS13 的分子功能仍然难以捉摸。遗传、功能和结构研究现已表明，VPS13 在细胞内细胞器之间的接触位点发挥作用，通过一种新机制运输脂质：通过跨越整个杆状 N 端半部的疏水通道在双层之间直接转移。与自噬蛋白 ATG2 的预测相似性表明 ATG2 具有类似的作用，现已通过结构和功能研究得到证实。在这里，在简要回顾这些证据后，我们讨论了人类 VPS13 蛋白在生理学和疾病中的已知信息。