# Junctophilin-2 cleavage in ischemic heart disease

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $586,411

## Abstract

PROJECT SUMMARY / ABSTRACT
Ischemic heart disease is a major cause of death in the United States. At the cellular level, myocardial
ischemia alters excitation-contraction coupling and promoted the development of heart failure. Junctophilin-2
(JPH2) is an inter-membrane linker protein that maintains the plasmalemma and sarcoplasmic reticulum (SR)
at a fixed distance to facilitate excitation-contraction coupling. Ischemia/reperfusion injury and ischemic heart
disease lead to a loss of JPH2 protein levels, which in part is caused by proteolysis by the Ca2+-sensitive
enzyme calpain. Our long-term goal of this project is to elucidate the molecular and cellular mechanisms by
which calpain causes JPH2 cleavage and how the ensuing JPH2 C-terminal peptide alters myocardial function.
We will test the central hypothesis that calpain cleaves JPH2 to release a C-terminal peptide that traffics into
the cardiomyocyte nucleus where it alters CaMKII-d splicing which affects myocardial remodeling.

## Key facts

- **NIH application ID:** 10375580
- **Project number:** 5R01HL153350-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Xander H.T. Wehrens
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $586,411
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375580

## Citation

> US National Institutes of Health, RePORTER application 10375580, Junctophilin-2 cleavage in ischemic heart disease (5R01HL153350-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10375580. Licensed CC0.

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