Introduction

McLeod syndrome and chorea-acanthocytosis (ChAc) constitute the classical syndromes known as "neuroacanthocytosis" (for recent reviews, see [8, 9, 42, 44]). While the genes altered in these diseases (XK and VPS13A, respectively) were identified several years ago [20, 26, 40], knowledge regarding the functions of the proteins encoded by these genes has proven to be slow and difficult to acquire. A generally accepted idea is that whatever the actual function of each of these proteins, a connection between them must exist in order to explain the similarity at the phenotypic level between both diseases. The neurological findings also resemble those of Huntington's disease, and a shared vulnerability of basal ganglia neurons due to mutations leading to these different syndromes has been proposed [9].

The function of XK is still unknown, although its structural features suggest that it is a membrane transport protein [20]. Its close interaction with Kell, a transmembrane protein with endothelin-3 converting activity, or, rather, the alteration of this interaction in McLeod syndrome, is a main focus of the basic research on this disease (see [28, 29] for a review). Here, we will address the possible function(s) of chorein, the protein encoded by the VPS13A gene that is altered in ChAc, and other similar proteins, in light of the data available so far.

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