Vps13 is a highly conserved lipid transfer protein found at multiple inter-organelle membrane contact sites where it mediates distinct processes. In yeast, recruitment of Vps13 to different contact sites occurs via various partner proteins. In humans, four VPS13 family members, A-D, are associated with different diseases. In particular, vps13A mutants result in the neurodegenerative disorder Chorea Acanthocytosis (ChAc). ChAc phenotypes resemble those of McLeod Syndrome, caused by mutations in the XK gene, suggesting that XK could be a partner protein for VPS13A. XK does, in fact, exhibit hallmarks of a VPS13A partner: it forms a complex with VPS13A in human cells and, when over-expressed, relocalizes VPS13A from lipid droplets to subdomains of the endoplasmic reticulum (ER). Introduction of two different ChAc disease-linked missense mutations into VPS13A prevents this XK-induced relocalization. These results suggest that dysregulation of a VPS13A-XK complex is the common basis for ChAc and McLeod Syndrome.

Vps13是高度保守的脂质转移蛋白，存在于多个细胞间膜接触部位，介导不同的过程。在酵母中，Vps13通过各种伴侣蛋白募集到不同的接触位点。在人类中，四个VPS13家族成员AD与不同的疾病有关。特别是，vps13A突变体会导致神经退行性疾病Chorea Acanthocytosis（ChAc）。ChAc表型类似于McLeod综合征，由XK突变引起基因，表明XK可能是VPS13A的伴侣蛋白。实际上，XK确实表现出VPS13A伴侣的特征：它在人细胞中与VPS13A形成复合物，并且当过表达时，会将VPS13A从脂质液滴重新定位到内质网（ER）的子域。将两个不同的ChAc疾病相关的错义突变引入VPS13A可防止这种XK诱导的重新定位。这些结果表明，VPS13A-XK复合物的失调是ChAc和McLeod综合征的常见基础。