# Zinc finger proteins (ZFPs) in health and disease

## TL;DR

This review explores how zinc finger proteins regulate gene expression and contribute to diseases like stroke, and evaluates new strategies to target them for therapy.

## Contribution

The paper introduces a comprehensive framework for targeting zinc finger proteins across multiple diseases, emphasizing ischemic stroke as a model.

## Key findings

- Zinc finger proteins regulate key stroke risk factors like hypertension and atherosclerosis.
- Dysregulated ZFP activity contributes to post-ischemic injury through neuroinflammation and cell death.
- Emerging therapies like PROTACs and ZFN-based gene editing offer promising ways to modulate ZFP function.

## Abstract

Zinc finger proteins (ZFPs), a vast superfamily of sequence-specific DNA and RNA-binding proteins, serve as master regulators of gene expression and cellular homeostasis. While traditionally studied for their roles in development, ZFPs have emerged as critical effectors and therapeutic targets across a wide spectrum of human pathologies, including cancer, neurological disorders, and autoimmune diseases. This review systematically dissects the molecular mechanisms by which dysregulated ZFP activity drives disease pathogenesis, using ischemic stroke as a central exemplar to illustrate their multifaceted roles. We detail how specific ZFPs orchestrate key stroke risk factors such as hypertension, hyperglycemia, and atherosclerosis, subsequently govern post-ischemic injury cascades, including neuroinflammation, programmed cell death, and blood–brain barrier disruption. Addressing the long-standing challenge of ZFPs as “undruggable” targets, we critically evaluate cutting-edge therapeutic strategies poised to modulate their function with precision. These include small-molecule modulators, targeted protein degraders (PROTACs), zinc finger nuclease (ZFN)-based gene editing, and advanced nanocarrier delivery systems, complemented by high-throughput computational screening. By integrating deep mechanistic insights with novel translational approaches, this review establishes a pioneering pan-disease framework for targeting ZFP networks. We provide a structured roadmap for future research and highlight the immense potential of ZFPs as a new class of master regulatory targets for developing novel and feasible therapies in ischemic stroke and beyond.