In a case of familial hypobetalipoproteinemia, resulting from heterozygosity for the pathogenic Gln845Argfs∗18 mutation in the ApoB gene, we showed that the resulting acanthocytes exhibited impaired cytoskeleton and membrane biophysical properties without significant loss of RBC functionality as assessed by functional tests applied on the total RBC population, without any distinction between acanthocytes and discocytes (e.g., osmotic fragility test, intracellular calcium measurement). The gene discussed is APOB; the disease is hypobetalipoproteinemia.