# Structural insights into Phospholipase Cε activity and regulation

## TL;DR

This paper reviews recent discoveries about PLCε, a key enzyme involved in cellular signaling and linked to kidney, pancreas, and cancer functions.

## Contribution

The paper provides a comprehensive summary of structural and functional advances in understanding PLCε regulation and its roles in health and disease.

## Key findings

- PLCε is involved in Ca2+-induced Ca2+-release in the kidneys and pancreas.
- PLCε plays a role in cancer progression through its signaling pathways.
- Structural studies reveal PLCε conformations in both basal and G protein-bound states.

## Abstract

Phospholipase Cε (PLCε) is a complex, multifunctional enzyme that responds to and integrates signals from G protein-coupled receptors and receptor tyrosine kinases through the direct binding of G proteins. These activators translocate PLCε to the cytoplasmic leaflets of the plasma and perinuclear membranes where the lipase hydrolyzes phosphatidylinositol lipids to produce inositol polyphosphates and diacylglycerol. These second messengers increase intracellular Ca2+ and/or activate protein kinase C, respectively, stimulating numerous pathways. Recent studies have broadened our understanding of this enzyme, revealing roles for PLCε in Ca2+-induced Ca2+-release processes in the kidneys and pancreas, as well as in cancer. These are complemented by structural studies that provide more complete insights into its basal and G protein-bound conformations. Here, we summarize and discuss these advances in understanding the regulation and roles of PLCε in normal and pathological contexts.