Language
English
Publication Date
6-4-2025
Journal
JACC: Basic to Translational Science
DOI
10.1016/j.jacbts.2025.03.004
PMID
40742358
Abstract
Junctophilin-2 (JPH2) is an essential structural protein that maintains the integrity of junctional membrane complexes (JMCs) in cardiomyocytes, thereby playing its canonical role in excitation-contraction (E-C) coupling. Recent studies reveal novel, nonstructural functions of JPH2 in cardiomyocytes, including regulation of mitochondrial function, lipid metabolism, nuclear signaling, and innate immune responses. Calpain-mediated cleavage of JPH2 generates nuclear fragments, which differentially modulate stress responses. Moreover, full-length JPH2 also localizes to the nucleus, where it forms phase-separated nuclear droplets during oxidative stress. Collectively, these findings highlight JPH2 as a multifunctional protein with critical roles beyond its canonical structural function in E-C coupling.
Keywords
cardiomyopathy, excitation-contraction coupling, heart failure, junctophilin, mitochondria, transverse tubule
Published Open-Access
yes
Recommended Citation
Hutchison, Daniel F; Lahiri, Satadru K; Prins, Kurt W; et al., "Nonstructural Roles of Junctophilin-2 in the Heart" (2025). Faculty and Staff Publications. 4025.
https://digitalcommons.library.tmc.edu/baylor_docs/4025