Evidence map›Paper›PMID 40249779›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

MFRP is a molecular hub that organizes the apical membrane of RPE cells by engaging in interactions with specific proteins and lipids.

Aleksander Tworak, Roman Smidak, Carolline Rodrigues Menezes, Samuel W Du, Susie Suh, Elliot H Choi, Sanae S Imanishi, Zhiqian Dong, Dominik Lewandowski, Kristen E Fong and 7 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Aleksander TworakDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Roman SmidakDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Carolline Rodrigues MenezesDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Samuel W DuDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.ORCID 0000-0002-9655-3659
Susie SuhDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.ORCID 0000-0002-4921-1429
Elliot H ChoiDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.ORCID 0000-0001-8762-5473
Sanae S ImanishiDepartment of Ophthalmology, and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Zhiqian DongDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Dominik LewandowskiDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.ORCID 0000-0002-2233-5501
Kristen E FongDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Gabriela GrigoreanProteomics Core Facility, Genome Center, University of California, Davis, CA 95616.
Antonio F M PintoClayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037.
Qianlan XuDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Dorota Skowronska-KrawczykDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.
Seth BlackshawDepartment of Ophthalmology, Johns Hopkins University, Baltimore, MD 21205.ORCID 0000-0002-1338-8476
Yoshikazu ImanishiDepartment of Ophthalmology, and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0003-4696-4836
Krzysztof PalczewskiDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697.ORCID 0000-0002-0788-545X

Funding

STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1M
NEI UCI Center Core Grant for Vision ResearchP30EY034070 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI James V Jester · 2022 to 2026
$3.7M
Membrane compartmentalization in photoreceptor health and diseaseR01EY036086 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI Yoshikazu Imanishi · 2024 to 2026
$1.6M
Photoreceptor dysfunction associated with rhodopsin mislocalizationR01EY028884 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI IMANISHI, YOSHIKAZU · 2018 to 2021
$1.6M
Correlating Genomic AMD Risk Variants with Lipid Composition and Phagocytic Function of Patient-Derived Induced Pluripotent Stem Cell (iPSC)-derived Retinal Pigment Epithelium (RPE)U01EY034594 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI SKOWRONSKA-KRAWCZYK, DOROTA, WAHLIN, KARL J · 2022 to 2025
$1.6M
microRNA-204 and microRNA-211 regulation of RPE phagocytosisF30EY033642 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Samuel Wang Du · 2022 to 2026
$241k
HHS | NIH (NIH) F30EY033642HHS | NIH (NIH) R01EY009339HHS | NIH (NIH) R01EY028884HHS | NIH (NIH) R01EY036086HHS | NIH (NIH) T32GM008620HHS | NIH (NIH) U01EY034594Knights Templar Eye Foundation (KTEF) 2023NEI NIH HHS F30 EY033642NEI NIH HHS P30 EY034070NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY028884NEI NIH HHS R01 EY036086NEI NIH HHS U01 EY034594NIGMS NIH HHS T32 GM008620
6 · The paper itself

Abstract

Membrane frizzled-related protein (MFRP), present in the retinal pigment epithelium (RPE), is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. While several preclinical gene-augmentation and gene-editing trials hold promise for future therapies aimed at stopping degeneration and restoring retinal function, the molecular mechanisms involved in MFRP biology are still not well understood. Here, we studied the biochemical properties of MFRP and the molecular consequences of its loss of function in the retinal degeneration 6 (rd6) mouse model. Using transcriptomic and lipidomic approaches, we observed that accumulation of docosahexaenoic acid (DHA) constitutes a primary defect in the MFRP-deficient RPE. In biochemical assays, we showed that MFRP undergoes extensive glycosylation, and it preferentially binds lipids of several classes, including phosphatidylserine and phosphatidylinositol-4-phosphate; as well as binding to several transmembrane proteins, notably adiponectin receptor 1 (ADIPOR1) and inward rectifier potassium channel 13 (KCNJ13). Moreover, MFRP determines the subcellular localization of ADIPOR1 and KCNJ13 in the RPE in vivo. This feature is altered by MFRP deficiency and can be restored by gene-therapy approaches. Overall, our observations suggest that MFRP constitutes an important interaction hub within the apical membrane of RPE cells, coordinating protein trafficking and subcellular localization within the RPE, and lipid homeostasis within the entire retina.

Indexed as

Cell MembraneMembrane ProteinsRetinal Pigment EpitheliumAnimalsDisease Models, AnimalDocosahexaenoic AcidsGlycosylationHumansLipid MetabolismMiceReceptors, AdiponectinRetinal DegenerationDocosahexaenoic AcidsMembrane ProteinsReceptors, AdiponectinlipidsMFRPretinaRPEvision

Identifiers

PMID40249779
PMCPMC12036977

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.