JPH3 and Huntington disease: HDL2 is a rare progressive and late-onset AD neurodegenerative disorder clinically resembling HD and caused by a monoallelic trinucleotide CTG/CAG repeat expansion located within the alternatively spliced exon 2A of JPH3. Overexpression of JPH3 transcripts containing an expanded CUG repeat expansion have been shown to cause cellular toxicity, suggesting that the RNA transcripts play an important role in the HDL2 pathogenesis via a toxic RNA gain-of-function effect [13]; however, also loss of full-length JPH3 protein expression has been potentially implicated in the disease pathogenesis [1].