# The role of nuclear envelope protein NET39 in skeletal muscle function and diseases

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $454,969

## Abstract

Project Summary/Abstract
Nuclear envelope proteins are essential for maintaining nuclear architecture, gene expression and chromatin
organization. Mutations in nuclear envelope proteins and nuclear lamins cause numerous human diseases,
many of which involve in skeletal muscle defects such as Emery-Dreifuss muscular dystrophy (EDMD). Although
the genetic mutations responsible for these diseases are known, the molecular mechanisms whereby
perturbations in the nuclear envelope cause disease are still not well understood. Moreover, it is still unclear why
mutations in ubiquitously expressed nuclear envelope proteins lead to tissue-specific pathogenesis such as
striated muscle-specific defects. Our lab recently showed that the nuclear envelope transmembrane protein 39
(NET39) is a muscle-specific regulator of nuclear envelope structure and function. NET39 is downregulated in
EDMD patient muscle biopsies, and deletion of Net39 in mice caused nuclear envelope deformations, congenital
myopathy and juvenile lethality. Within the nuclear envelope, NET39 interacts with several components of the
nuclear envelope such as LEMD2. Our studies of NET39 provide an entry point to unravel the long-standing
puzzle of why striated muscle is specifically affected in nuclear envelope related diseases. We hypothesize that
NET39 plays a pivotal skeletal muscle-specific role in the pathogenesis of EDMD. The overall goals of this project
are to define the functions of NET39 and its interactions with other nuclear envelope proteins in regulating nuclear
envelope integrity and gene expression during skeletal muscle homeostasis and disease, and to explore the role
of NET39 in EDMD and other laminopathies. Ultimately, we hope to use these insights to develop new
therapeutic strategies for EDMD and related laminopathies.

## Key facts

- **NIH application ID:** 10812456
- **Project number:** 5R01AR080676-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Ning Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,969
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812456

## Citation

> US National Institutes of Health, RePORTER application 10812456, The role of nuclear envelope protein NET39 in skeletal muscle function and diseases (5R01AR080676-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10812456. Licensed CC0.

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