The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology

Laura Lagostena1, Velia Minicozzi2, Martina Meucci3

  • 1Institute of Biophysics, National Research Council, Via De Marini 6, 16149 Genova, Italy.

Insights

Two-pore channel 2 (TPC2) is an endolysosomal ion channel crucial for cell signaling and disease. This review details TPC2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Pharmacology

Background:

  • Two-pore channel 2 (TPC2) is an endolysosomal ion channel.
  • It plays key roles in intracellular calcium signaling and endomembrane dynamics.
  • Dysregulation of TPC2 is implicated in various human diseases.

Purpose of the Study:

  • To provide an in-depth analysis of TPC2's structure, function, and physiological roles.
  • To explore TPC2's involvement in human diseases, including viral infections and cancer.
  • To review current methodologies for studying TPC2 and its potential as a drug target.

Main Methods:

  • Review of existing literature on TPC2.
  • Analysis of structural determinants of ion permeation.
  • Examination of experimental approaches like heterologous expression and computational modeling.

Main Results:

  • TPC2's structure, including the selectivity filter and central cavity, influences channel kinetics.
  • Emerging roles of TPC2 in SARS-CoV-2 infection, melanoma, and neoangiogenesis are highlighted.
  • Natural compounds like naringenin show inhibitory potential against TPC2.

Conclusions:

  • TPC2 is a critical regulator of cellular processes with significant implications in disease.
  • Understanding TPC2's structure-function relationship is key to developing targeted therapies.
  • TPC2 represents a promising pharmacological target for infectious and neoplastic diseases.

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