# p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials

## TL;DR

This paper reviews how the p63 gene helps maintain healthy skin and contributes to skin diseases, focusing on its different forms and roles in development and disease.

## Contribution

The paper provides a comprehensive review of p63's molecular mechanisms and dual roles in skin health and disease, emphasizing its therapeutic potential.

## Key findings

- p63 regulates skin development through epithelial fate determination and barrier formation.
- Mutations in p63 are linked to ectodermal dysplasia and other skin disorders.
- p63 isoforms TAp63 and ΔNp63 have distinct roles in cell proliferation and stress responses.

## Abstract

As a pivotal member of the p53 family, the p63 gene plays an indispensable role in skin homeostasis and development. The gene encodes multiple isoforms, primarily TAp63 and ΔNp63, which differentially regulate cell proliferation, differentiation, and stress responses through complementary mechanisms. This comprehensive review systematically examines the molecular mechanisms and cellular functions of p63 in cutaneous biology, with particular emphasis on its dual roles in maintaining skin integrity and contributing to disease pathogenesis. We detail the essential functions of p63 in skin development, encompassing epithelial fate determination, chromatin remodeling, cell adhesion, and barrier formation, while also exploring its involvement in skin regeneration and differentiation via metabolic reprogramming and stem cell modulation. Furthermore, we analyze how mutations in p63 underlie ectodermal dysplasia and various dermatological disorders, underscoring the gene’s fundamental importance in cutaneous health. By integrating current knowledge of the diverse biological roles of p63 and its associated therapeutic potential as a target, this review highlights its central significance in both skin physiology and pathology.