# FAM26F function and role in macrophages

> **NIH NIH R03** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $169,500

## Abstract

Abstract
Ion channels, transporters, exchangers and pumps (here called ICTs) control most aspects of life. They have
been extensively characterized in excitable cells, such as neurons, where they control neurotransmitter release
and other functions as well as cardiac and skeletal muscle cells, where they regulate the strength of contraction.
In most non-excitable cells, and specifically in immune cells, ICTs are only scantly characterized. We have taken
a global approach to analyze the expression of more than 600 ICTs in immune cells, and observed that one
particular putative ICT, named FAM26F, is highly and specifically expressed in proinflammatory macrophages
compared to other immune cells. FAM26F is an understudied ion channel that belongs to a small family of
proteins (FAM26A to F). The best characterized FAM26 family member is FAM26C. It functions as an ion channel
under certain experimental conditions and has been described to promote ATP release from cells. Recently
published low resolution structures of FAM26F show that it, like FAM26C, also forms a pore and may act as an
ion channel. Our preliminary data to date, however, did not detect evidence for channel function of FAM26F
when overexpressed in mammalian cells. The most likely reason is that FAM26F needs other subunits or
associated proteins to function as a channel, which is characteristic of many ion channels. We hypothesize that
while overexpression of FAM26F may not be sufficient to generate a functional channel, and proinflammatory
macrophages express not only FAM26F but also the other proteins required to form a channel. To test this
hypothesis, we will in Aim 1 directly measure putative functions of FAM26F such as channel currents and the
transport of low molecular weight molecules. In a parallel approach, we will use biochemical methods and mass
spectrometry to identify the proteins that associate with FAM26F in macrophages. In Aim 2, we will elucidate the
role of FAM26F in macrophage function and inflammation. Our preliminary data have shown that deletion of
FAM26F impairs certain proinflammatory functions of macrophages such as the release of cytokines. These
immune messenger proteins are critical for disease progression in the autoimmune disease rheumatoid arthritis,
where they drive joint inflammation and destruction. We will therefore use macrophages and mice in which
FAM26F has been deleted to determine the effects of FAM26F on macrophage function in cell culture settings
and in mouse models of rheumatoid arthritis. This multi-PI R03 proposal by Drs. Stefan Feske and William
Coetzee brings together their unique expertise to better understand the roles of channels, and in particular
FAM26F, in innate immunity. There are currently no FDA approved drugs that target ion channels for
immunological disorders and the completion of the proposed studies takes us an important step in the direction
of this missed therapeutic opportunity.

## Key facts

- **NIH application ID:** 10449780
- **Project number:** 1R03TR004157-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** William A Coetzee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $169,500
- **Award type:** 1
- **Project period:** 2022-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449780

## Citation

> US National Institutes of Health, RePORTER application 10449780, FAM26F function and role in macrophages (1R03TR004157-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10449780. Licensed CC0.

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