Molecular functions of ANKLE2 and its implications in human disease

• Published in: Disease models & mechanisms Vol. 17; no. 4
• Main Authors: Fishburn, Adam T, Florio, Cole J, Lopez, Nick J, Link, Nichole L, Shah, Priya S
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-04-2024; The Company of Biologists
• Subjects: Animals; cell division; Disease; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Humans; microcephaly; Mutation - genetics; neurodevelopment; Nuclear Proteins - metabolism; Review; Cell division; Neurodevelopment; Microcephaly
• ISSN: 1754-8403; 1754-8411; 1754-8411
• DOI: 10.1242/dmm.050554

Ankyrin repeat and LEM domain-containing 2 (ANKLE2) is a scaffolding protein with established roles in cell division and development, the dysfunction of which is increasingly implicated in human disease. ANKLE2 regulates nuclear envelope disassembly at the onset of mitosis and its reassembly after chromosome segregation. ANKLE2 dysfunction is associated with abnormal nuclear morphology and cell division. It regulates the nuclear envelope by mediating protein-protein interactions with barrier to autointegration factor (BANF1; also known as BAF) and with the kinase and phosphatase that modulate the phosphorylation state of BAF. In brain development, ANKLE2 is crucial for proper asymmetric division of neural progenitor cells. In humans, pathogenic loss-of-function mutations in ANKLE2 are associated with primary congenital microcephaly, a condition in which the brain is not properly developed at birth. ANKLE2 is also linked to other disease pathologies, including congenital Zika syndrome, cancer and tauopathy. Here, we review the molecular roles of ANKLE2 and the recent literature on human diseases caused by its dysfunction.