# Regulation of lipin phosphatidic acid phosphatase activity

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $376,709

## Abstract

Project Summary/Abstract
It has been more than 50 years since Eugene Kennedy described/identified phosphatidic acid
phosphatase (PAP) activity. This enzymatic activity unified what is now known as the Kennedy
pathway of phosphatidylcholine synthesis. The genes encoding PAP, termed Lipin 1-3, sit at an
important branch point in the Kennedy pathway of glycerolipid synthesis. Unlike the remainder
of the enzymes in the triacylglycerol synthesis pathway, the lipins are cytosolic proteins that
translocate from the cytosol to their site of action at internal membranes. Loss of function alleles
of lipin family members results in profound metabolic and inflammatory disturbances in both
mice and humans, and lipin polymorphisms are linked to a number of metabolic conditions.
But while genetics has demonstrated the importance of these enzymes in health and disease,
precisely how they are regulated is still poorly defined. Elucidating the mechanisms and
pathways controlling lipin family activity will provide insight into glycerolipid biosynthesis and
the pathophysiological consequences when it is disrupted, and will open new avenues for
pharmacological interventions for these diseases. This proposal undertakes a rigorous and
comprehensive examination of lipin 1 regulation with the goal of understanding how its PAP
activity is biochemically controlled. We will characterize the effects of two kinases on lipin 1 PAP
activity and stability and identify how these regulatory events occur. In addition, we will
determine how dysregulation of lipin PAP activity impacts cellular function, particularly neutral
and phospholipid synthesis. Given the striking phenotypes displayed by genetic alterations in
the lipins, accomplishing these aims will yield important insights into lipid biosynthetic
pathways as well as clinically relevant pathologies.

## Key facts

- **NIH application ID:** 9943978
- **Project number:** 1R01GM136900-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Thurl E. Harris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,709
- **Award type:** 1
- **Project period:** 2020-03-10 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9943978

## Citation

> US National Institutes of Health, RePORTER application 9943978, Regulation of lipin phosphatidic acid phosphatase activity (1R01GM136900-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9943978. Licensed CC0.

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