Junctophilin-1 (JPH1)

Junctophilin-1 (JPH1) is a non-enzymatic, structural membrane protein essential for the formation and maintenance of junctional membrane complexes, particularly the triad structure in skeletal muscle. By spanning and physically linking the plasma membrane (sarcolemma) and the endoplasmic/sarcoplasmic reticulum, it ensures proper spatial arrangement for excitation–contraction coupling, facilitating calcium signaling between the surface and internal calcium stores in muscle cells. JPH1 directly interacts with the L-type calcium channel (Cav1.1) and the ryanodine receptor 1 (RyR1), crucial for muscle contraction, and also binds caveolin-3. JPH1 is the primary junctophilin isoform in skeletal muscle, with much lower levels in the heart. Mutations or loss of JPH1 lead to disorganization and loss of muscle triads, resulting in defective muscle contraction and contributing to rare human muscle diseases. Junctophilin-1 is a highly conserved structural protein, not a typical “therapeutic target” such as a receptor, enzyme, or transporter. There are currently no known drugs or direct pharmacological modulators of JPH1. Its disease relevance is due to congenital or inherited mutations affecting muscle structure and function.

Other names

Junctophilin type 1JP-1JP1junctophilin1junctophilin-1CMT2KCMYO25

None known (not a direct drug target)