# Molecular Mechanism of ROMK Channel Function

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $506,175

## Abstract

ROMK (Kir 1.1, product of the KCNJ1 gene) channels in the kidney are
exquisitely regulated to adjust renal potassium excretion and maintain potassium
balance. Clathrin-dependent endocytosis plays a critical role, limiting urinary potassium
loss in potassium deficiency. In renal disease, aberrant ROMK endocytosis may
contribute to potassium retention and life-threatening hyperkalemia. Available evidence
indicates ROMK endocytosis is stimulated by WNKs, kinases that are mutated in
Familial Hyperkalemic and Hypertension (FHHt). This application builds on our recent
discoveries that: 1) Low potassium directly stimulates ROMK endocytosis in the distal
nephron, 2) WNK stimulates ROMK endocytosis by phosphorylating the clathrin-adaptor,
ARH, 3) NEDD4 Family of Interacting Proteins, NDFIP1 and 2, interact with ROMK to
control post-endocytic processing of the channel. To carry these breakthrough
observations toward a completely new understanding of how potassium balance is
achieved, we outline plans to: 1) Define the mechanism by which potassium directly
regulates ROMK endocytosis; 2) Explore the involvement of this pathway in a mouse
model of FHHt, 3) Elucidate the molecular mechanism by which NDFIP1 and NDFIP2
control post-endocytic routing of ROMK to the lysosome. The studies should provide
novel insights into the molecular basis of renal K handling and K homeostasis in health
and disease while illuminating fundamental mechanisms of membrane protein targeting
in the kidney.

## Key facts

- **NIH application ID:** 9897412
- **Project number:** 5R01DK054231-20
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Paul A Welling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $506,175
- **Award type:** 5
- **Project period:** 2019-10-05 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897412

## Citation

> US National Institutes of Health, RePORTER application 9897412, Molecular Mechanism of ROMK Channel Function (5R01DK054231-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9897412. Licensed CC0.

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