# How skin achieves mechano-resistance for land movement: the critical role of ER sensing

## TL;DR

This paper explores how skin evolved to resist mechanical stress, focusing on a protein called SLURP1 that helps protect skin cells during movement on land.

## Contribution

The study identifies SLURP1 as a novel ER protein that prevents mechanical stress in skin cells by maintaining SERCA2b activity and inhibiting pPERK-NRF2 signaling.

## Key findings

- SLURP1 preserves SERCA2b activity in palmoplantar keratinocytes under mechanical pressure.
- SLURP1 inhibits pPERK-NRF2 signaling to protect skin cells from mechanical stress.
- The protein plays a critical role in enabling skin to withstand body weight during terrestrial movement.

## Abstract

To adapt to gravitational forces during the transition to terrestrial life, animals evolved specialized paw skin to withstand their body weight and allow for locomotion. In a recent Cell article, Di et al. demonstrate SLURP1 as an endoplasmic reticulum (ER) membrane protein that protects palmoplantar keratinocytes from mechanical stress by preserving SERCA2b activity and inhibiting the pPERK-NRF2 signaling under mechanical pressure.