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<p>Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a newly discovered histidine phosphatase that can remove histidine-linked phosphate groups from proteins, but its function is unclear. Given that the LHPP protein might participate in histidine phosphorylation, it is receiving increasing attention from researchers. Recent evidence has suggested that LHPP is a novel tumor suppressor with a crucial role in cancers, as its expression is decreased in different cancers. Previous studies have confirmed that abnormal LHPP levels can lead to overactivation of pathways such as the PI3K/AKT pathway during the course of tumor pathogenesis. In addition, LHPP has been confirmed as a susceptibility gene for depression, which has triggered many related studies. However, the current understanding of the functions of LHPP in diseases is relatively limited, and a systematic summary of its mechanism is lacking. Therefore, this paper reviews relevant studies of LHPP to clarify the mechanism of its involvement in cancers and nervous system diseases and provides new strategies for disease research involving LHPP.</p>

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Advances in signaling pathway networks involving LHPP in various diseases

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Xuan Cai,
  • Yalin Zhang,
  • Lu Zhao,
  • Qing Chang,
  • Yuhong Zhao,
  • Zhuxi Liu

摘要

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a newly discovered histidine phosphatase that can remove histidine-linked phosphate groups from proteins, but its function is unclear. Given that the LHPP protein might participate in histidine phosphorylation, it is receiving increasing attention from researchers. Recent evidence has suggested that LHPP is a novel tumor suppressor with a crucial role in cancers, as its expression is decreased in different cancers. Previous studies have confirmed that abnormal LHPP levels can lead to overactivation of pathways such as the PI3K/AKT pathway during the course of tumor pathogenesis. In addition, LHPP has been confirmed as a susceptibility gene for depression, which has triggered many related studies. However, the current understanding of the functions of LHPP in diseases is relatively limited, and a systematic summary of its mechanism is lacking. Therefore, this paper reviews relevant studies of LHPP to clarify the mechanism of its involvement in cancers and nervous system diseases and provides new strategies for disease research involving LHPP.