JPH4 (junctophilin 4) is a brain-specific membrane protein that forms junctional complexes between the endoplasmic reticulum (ER) and plasma membrane in neurons. JPH4 creates ER-plasma membrane junctions through its C-terminal transmembrane domain anchored in the ER and N-terminal domains that bind to the plasma membrane 1. In hippocampal CA1 pyramidal cells, JPH4 works together with JPH3 to tether a tripartite complex containing Cav1.3/Cav1.2 calcium channels, RyR2 ryanodine receptors, and KCa3.1 potassium channels, which is essential for regulating neuronal excitability through the slow afterhyperpolarization (sAHP) 2. JPH4 can recruit high-voltage-activated calcium channels to junctions and modulate their inactivation kinetics, particularly for CaV2.1 channels through interactions with the II-III loop domain 13. Unlike other junctophilins, JPH4 does not support voltage-induced calcium release, as JPH4-induced ER-plasma membrane junctions contain CaV1.1 but exclude RYR1 channels 4. The protein appears to have broader physiological relevance, with recent studies identifying JPH4 as a potential biomarker in various disease contexts 56, though its specific role in these conditions requires further investigation.