In HD, the Huntingtin (Htt) protein accumulates gradually in cells, forming large molecules that accumulate in the brain, affecting the function of nerve cells, and resulting in the progressive death of the striatum and cortical nerve cells. lncRNA HttAS_v1 is an antisense transcript of the Htt gene and is expressed at a low level in the frontal cortex of HD patients, leading to high expression of Htt mRNA, which in turn promotes HD pathogenesis.36 Htt modulates the nuclear translocation of the transcriptional repressor RE1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). Mutant Htt promotes abnormal nuclear-cytoplasmic transport of REST/NRSF and then leads to abnormal expression of REST target genes, including protein-coding and non-coding genes (Figure 2).37, 38Figure 2Role of the lncRNA HttAS-v1 in HDThe expression of HttAS-v1 is decreased in HD patients, resulting in high expression of Htt mRNA. Htt is involved in the translocation of REST/NRSF into the nucleus, retaining REST/NRSF in the cytosol and thereby preventing REST/NRSF target gene repression.