Junctophilin-3 (JPH3)

Junctophilin-3 (JPH3) is a membrane-associated scaffold protein encoded by the JPH3 gene, primarily expressed in the brain, especially in neurons involved in motor coordination and memory[1][2][4]. It is a member of the junctophilin family, whose proteins form junctional membrane complexes linking the plasma membrane with the endoplasmic reticulum, facilitating precise calcium ion signaling essential for neuronal excitability and function[1][2][3][4][5]. The JPH3 gene contains a CAG/CTG trinucleotide repeat, and expansion of this repeat causes Huntington's disease-like 2 (HDL2), a rare neurodegenerative disorder clinically similar to Huntington’s disease[1][2][4]. In the context of cancer, JPH3 has been identified as a methylated tumor suppressor gene in colorectal and gastric cancers; loss or silencing of JPH3 promotes cancer cell proliferation and migration, while its re-expression induces apoptosis through mitochondrial pathways, partly by altering calcium homeostasis[5]. As of this writing, no approved drugs are known to target JPH3 directly, and it serves as a genetic and epigenetic biomarker for certain disorders[5].

Other names

Junctophilin 3JP3TNRC22JP-3CAGL237HDL2Junctophilin type 3Trinucleotide repeat-containing gene 22 proteintrinucleotide repeat containing 22junctophilin3