Junctophilin-3 (JPH3) is a protein residing in humans that is encoded by the JPH3 gene. The gene is approximately 97 kilobases long and is located at chromosomal position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexes, which link the plasma membrane with the endoplasmic reticulum in excitable cells. JPH3 is localized to the brain and is associated with motor coordination and memory neurons. The protein contains 748 residues and is composed of a C-terminal hydrophobic segment that spans the endoplasmic/sarcoplasmic reticulum membrane and a cytoplasmic domain that displays specific affinity for the plasma membrane, as well as several membrane occupation and recognition nexus repeats involved in plasma membrane binding through interactions with phospholipids. JPH3 is primarily expressed in the brain, specifically in the dorsolateral prefrontal cortex. Although the precise function of the protein has not been determined, it has been shown to play a role in motor coordination and memory through calcium ion signaling and the stabilization of neuronal cellular architecture. The JPH3 gene contains a CAG/CTG trinucleotide repeat segment. Expansion of this segment in various genes can cause polyglutamine diseases. The expansion of the CAG tandem repeat in JPH3 is associated with the HDL2's type of Huntington's disease-like syndrome. The pathological expansion of the CAG repeat region leads to an expanded polyglutamine tract, which can aggregate in neurons, leading to the degeneration of neuronal subpopulations.