HTT encodes huntingtin, a large ubiquitous protein that promotes autophagosome formation and regulates multiple cellular processes including vesicle transport, organelle organization, and DNA repair. The protein interacts with numerous binding partners including dynactin, dynein, and DNA repair proteins MLH1 and exonuclease 1, functioning to stabilize MLH1 and suppress excessive DNA end resection during double-strand break repair 1. HTT is distributed throughout subcellular compartments and plays roles in establishing mitotic spindle orientation and maintaining cellular homeostasis 2. Pathogenic CAG repeat expansions in HTT cause Huntington's disease, where the expanded polyglutamine stretch confers toxic properties leading to neurodegeneration 3. Multiple clinical features including age of onset, motor dysfunction, and cognitive deficits correlate with CAG repeat length 4. The mutant protein loses normal regulatory functions, causing MLH1 degradation, DNA hyperexcision, and activation of cGAS-STING-dependent apoptosis 1. Recent studies demonstrate that both loss of normal HTT function and gain-of-toxic function mechanisms contribute to disease pathology 5. Therapeutically, HTT-lowering approaches show promise, with drugs like tominersen and PTC518 demonstrating dose-dependent reductions in HTT mRNA and protein levels in clinical trials 6. RNA-targeting CRISPR/CasRx systems also show efficacy in preclinical models, reducing mutant HTT expression and ameliorating disease symptoms 7.