TTPA encodes alpha-tocopherol transfer protein, which binds alpha-tocopherol and facilitates its transfer between cellular membranes and release from hepatocytes [PubMed:7887897]. The protein exhibits lipid transfer activity and binds phosphatidylinositol bisphosphates, with conformational changes induced by these interactions promoting alpha-tocopherol release. TTPA is essential for systemic vitamin E distribution to peripheral tissues including the brain, heart, muscle, and adipose tissue. Genetic defects in TTPA cause ataxia with vitamin E deficiency (AVED), an autosomal recessive cerebellar ataxia characterized by progressive neurodegeneration 1. The c.744delA frameshift mutation represents the most frequent TTPA pathogenic variant, particularly in Tunisian populations. TTPA knockout mice (Ttpa-/-) demonstrate severe systemic alpha-tocopherol depletion, with undetectable levels in brain, muscle, and serum, while retaining only residual tissue stores 2. Clinically, alpha-tocopherol deficiency manifests as spinocerebellar ataxia, peripheral neuropathy, myopathy, and impaired immune function 2. TTPA-deficient mice exhibit exacerbated inflammatory responses and reduced grip strength following systemic lipopolysaccharide administration, suggesting vitamin E deficiency increases vulnerability to inflammatory stress. TTPA function is therefore critical for maintaining adequate antioxidant capacity and neurological health.