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

## TL;DR

This review explores TPC2, an ion channel involved in calcium signaling and disease, highlighting its role in viral infections and cancer, and its potential as a drug target.

## Contribution

The paper provides a comprehensive overview of TPC2's structure, function, and pharmacological potential in diseases.

## Key findings

- TPC2 is involved in intracellular calcium signaling and endomembrane dynamics.
- TPC2 contributes to melanoma progression and SARS-CoV-2 infection.
- Natural compounds like naringenin show inhibitory potential against TPC2.

## Abstract

Two-pore channel 2 (TPC2) is a member of the endolysosomal ion channel family, playing critical roles in intracellular calcium signaling and endomembrane dynamics. This review provides an in-depth analysis of TPC2, covering its structural and functional properties, physiological roles, and involvement in human diseases. We discuss current experimental approaches to studying TPC2, including heterologous expression in plant vacuoles and computational modeling strategies. Particular emphasis is placed on the structural determinants of ion permeation, with a focus on the selectivity filter and the central cavity’s influence on channel kinetics. Furthermore, we explore emerging roles of TPC2 in viral infections, particularly SARS-CoV-2, and in cancer, including melanoma progression and neoangiogenesis. The inhibitory potential of natural compounds, such as naringenin, is also examined. By offering a comprehensive overview of current knowledge and methodologies, this review underscores the potential of TPC2 as a promising pharmacological target in both infectious and neoplastic diseases.