Open Access

REVIEW

Heavy Metal-Associated Isoprenylated Plant Proteins (HIPPs): Multifunctional Regulators of Metal Homeostasis, Abiotic/Biotic Stress Responses, and Plant Development

Shi Xu¹, Jingjing Sun¹, Jiayi Ji¹, Junhao Huang¹, Yiyong Zhu², Haidong Ding¹, Ming Ding^1,*

1 College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China
2 College of Resource and Environment Science, Nanjing Agricultural University, Nanjing, China

* Corresponding Author: Ming Ding. Email:

(This article belongs to the Special Issue: Membrane Transporters in Plant Stress Adaptation)

Phyton-International Journal of Experimental Botany 2026, 95(7), 4 https://doi.org/10.32604/phyton.2026.086430

Received 30 May 2026; Accepted 06 July 2026; Issue published 30 July 2026

Abstract

Heavy metal-associated isoprenylated plant proteins (HIPPs) are a class of vascular plant specific metallochaperones, characterized by the presence of one or two N-terminal heavy metal-associated (HMA) domains and a C-terminal isoprenylation motif (CaaX). The HMA domain contains a conserved CysXXCys motif that is responsible for binding transition metals such as Cd²⁺, Cu²⁺, Zn²⁺ and Pb²⁺. The CaaX motif modulates post-translational prenylation that anchors HIPPs to membranes and facilitates protein-protein interactions. This review systematically summarizes the structural features and multifaceted functions of HIPPs in plants. Beyond their well known function in heavy metal detoxification, HIPPs are more recently recognized as key regulators of abiotic stress responses, including drought, cold, and salinity, and biotic stress resistance via interactions with pathogen effectors. Moreover, HIPPs also participate in plant growth and development and in hormone signaling, including the cytokinin and abscisic acid (ABA) pathways. Translating this knowledge holds great promise for developing stress-tolerant crop varieties, breeding low-cadmium crops, and advancing phytoremediation technologies.

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