Junctophilin-4 (JPH4)

Junctophilin-4 is a member of the junctophilin family of transmembrane proteins that are essential for forming junctional membrane complexes (JMCs) in excitable cells, especially neurons. These proteins tether the plasma membrane to the endoplasmic or sarcoplasmic reticulum, enabling functional cross-talk required for calcium signaling. Junctophilin-4, encoded by the JPH4 gene, contains eight membrane occupation and recognition nexus (MORN) motifs that facilitate its attachment to phospholipids and a C-terminal membrane-spanning region that anchors it in the ER membrane. In excitable cells, it plays a structural and regulatory role in store-operated calcium entry (SOCE) by recruiting STIM1 and Orai1 to ER–PM contact sites. Junctophilin-4 is brain-specific in expression but also found in T cells, where it supports Ca²⁺ homeostasis and SOCE activation. Mutations or dysregulation of junctophilin-4, especially in combination with related family members, are associated with neurodegenerative and muscle diseases[1][2][3][4][5].

Other names

Junctophilin 4JPH4JPHL1JP-4JP4junctophilin-like 1 proteinKIAA1831