Huntingtin protein (mutant form) (HTT (or mHTT for mutant huntingtin))

The mutant form of the *huntingtin protein* (mHTT) is the pathogenic cause of Huntington’s disease, produced from the *HTT* gene carrying an expanded CAG repeat coding for a polyglutamine (polyQ) tract in its N-terminal region[2][6][7][8]. Mutant huntingtin is a large cytoplasmic protein (~348–350 kDa) with a predominantly α-helical, HEAT repeat-containing scaffold structure[2][6]. The pathogenic polyQ expansion (>35–40 repeats) causes abnormal aggregation, disrupts vesicular and mitochondrial transport, alters gene expression, increases oxidative stress, and eventually leads to selective neuronal death in the striatum and cortex[2][3][6][8]. mHTT is a validated therapeutic target in Huntington’s disease, with disease-modifying therapies aimed at reducing its expression or preventing its toxic effects in clinical development. The wild-type protein plays important roles in vesicular trafficking, cytoskeletal dynamics, and transcriptional regulation, so selective targeting of only the mutant form is an important safety consideration[7][8].

Other names

Mutant huntingtinmHTTHTT (when referring to mutant allelic form)Huntingtin with expanded polyglutamine tractMutant huntingtin protein

RNA interference or antisense-mediated mRNA degradation (reducing HTT protein levels); Splicing modulation to reduce mutant protein formation; Gene silencing by DNA-directed gene editing; Direct inhibition of protein aggregation/toxicity (experimental)