AUTHOR=Almannai Mohammed , Marafi Dana , El-Hattab Ayman W. 

TITLE=WIPI proteins: Biological functions and related syndromes

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=15

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.1011918

DOI=10.3389/fnmol.2022.1011918

ISSN=1662-5099

ABSTRACT=<p>WIPI (<italic>W</italic>D-repeat protein <italic>I</italic>nteracting with <italic>P</italic>hospho<italic>I</italic>nositides) are important effectors in autophagy. These proteins bind phosphoinositides and recruit autophagy proteins. In mammals, there are four WIPI proteins: WIPI1, WIPI2, WIPI3 (WDR45B), and WIPI4 (WDR45). These proteins consist of a seven-bladed β-propeller structure. Recently, pathogenic variants in genes encoding these proteins have been recognized to cause human diseases with a predominant neurological phenotype. Defects in <italic>WIPI2</italic> cause a disease characterized mainly by intellectual disability and variable other features while pathogenic variants in <italic>WDR45B</italic> and <italic>WDR45</italic> have been recently reported to cause El-Hattab-Alkuraya syndrome and beta-propeller protein-associated neurodegeneration (BPAN), respectively. Whereas, there is no disease linked to <italic>WIPI1</italic> yet, one study linked it neural tube defects (NTD). In this review, the role of WIPI proteins in autophagy is discussed first, then syndromes related to these proteins are summarized.</p>