Huntingtin

Huntingtin (HTT) is a large cytoplasmic protein of 3,142 amino acids that may regulate microtubule-mediated transport and vesicle trafficking, and promotes the formation of autophagic vesicles (UniProt: P42858). The protein is best known for its association with Huntington disease, a progressive neurodegenerative disorder caused by polyglutamine repeat expansion, characterized by chorea, motor impairment, psychiatric symptoms, and dementia with selective neuronal loss in the striatum.

In the context of Alzheimer's disease, Huntingtin shows consistent downregulation in post-mortem AD brain tissue compared to age-matched controls across multiple subcellular fractions (mean log2FC −0.53; Chaparral AD proteomics). This reduction was observed in a TMT-labeled quantitative proteomics study examining four subcellular compartments from human brain samples. The functional significance of reduced Huntingtin levels in AD pathology remains to be elucidated, though the protein's roles in autophagy and vesicular transport suggest potential relevance to protein clearance mechanisms implicated in neurodegeneration.