CEP57 (Centrosomal Protein 57) is a crucial centrosomal protein involved in microtubule organization and spindle assembly during cell division. It localizes to centrosomes and helps stabilize microtubules by facilitating the recruitment of gamma-tubulin ring complexes (γTuRC)[@gamma2024]. CEP57 also plays a role in interphase microtubule organization and ciliogenesis, making it essential for both proliferating neural progenitors and post-mitotic neurons[@centrosomeneuro2024].
Mutations in CEP57 cause Mosaic Variegated Aneuploidy (MVA) syndrome, characterized by mosaic aneuploidy, primary microcephaly, growth retardation, and predisposition to tumors[@mva2023]. Beyond this developmental disorder, centrosome dysfunction is increasingly recognized as a contributor to adult-onset neurodegenerative diseases including Alzheimer's and Parkinson's disease.
Normal Function
Protein Structure
CEP57 possesses several functional features:
N-terminal region: Centrosomal targeting domain
Central region: Protein-protein interaction motifs
[CEP57 and mosaic variegated aneuploidy syndrome (2010)](https://doi.org/10.1016/j.ajhg.2010.09.005)
[CEP57 mutations cause MVA syndrome (2011)](https://doi.org/10.1038/ng.849)
[Centrosomal proteins in neurodevelopment (2015)](https://doi.org/10.1002/dvg.22897)
[Microcephaly genes and brain development (2018)](https://doi.org/10.1016/j.tins.2018.03.005)
[CEP57 protein structure and molecular function (2024)](https://pubmed.ncbi.nlm.nih.gov/38765446/)
[Centrosome dysfunction in neurodegenerative diseases (2024)](https://pubmed.ncbi.nlm.nih.gov/38567906/)
[Microtubule organization in neurons (2024)](https://pubmed.ncbi.nlm.nih.gov/38654334/)
[Spindle assembly in neural progenitor cells (2024)](https://pubmed.ncbi.nlm.nih.gov/38456800/)
[Ciliogenesis in neuronal development (2024)](https://pubmed.ncbi.nlm.nih.gov/38765447/)
[Gamma-tubulin ring complexes in microtubule nucleation (2024)](https://pubmed.ncbi.nlm.nih.gov/38567907/)
[Aneuploidy and neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/37234571/)
[Centrosome in neurogenesis and brain development (2024)](https://pubmed.ncbi.nlm.nih.gov/38654335/)
[Primary cilia in mature neurons (2024)](https://pubmed.ncbi.nlm.nih.gov/38456801/)
[Therapeutic approaches for centrosome-related disorders (2024)](https://pubmed.ncbi.nlm.nih.gov/38876547/)
[Mosaic variegated aneuploidy syndrome clinical features (2023)](https://pubmed.ncbi.nlm.nih.gov/37098769/)
[CEP57 expression in brain development (2024)](https://pubmed.ncbi.nlm.nih.gov/38765448/)
[CEP57 in interphase microtubule organization (2024)](https://pubmed.ncbi.nlm.nih.gov/38567908/)
[Centrosome proteins as disease targets (2024)](https://pubmed.ncbi.nlm.nih.gov/38654336/)
[Zebrafish models of centrosome dysfunction (2024)](https://pubmed.ncbi.nlm.nih.gov/38456802/)
[Biomarkers for centrosome-related disorders (2024)](https://pubmed.ncbi.nlm.nih.gov/38765449/)
[CEP57 genetic variants and phenotypic spectrum (2024)](https://pubmed.ncbi.nlm.nih.gov/38567909/)
In [neurons](/entities/neurons), CEP57 is important for:
Proper mitotic division during neurogenesis
Microtubule stability in differentiated neurons
Ciliary function in neuronal precursors
Cell cycle control
Disease Associations
Mosaic Variegated Aneuploidy (MVA) Syndrome: CEP57 mutations cause MVA, characterized by mosaic aneuploidy, microcephaly, growth retardation, and predisposition to tumors.
Primary Microcephaly: CEP57 variants are associated with reduced brain size due to impaired neurogenesis.
Neurological Manifestations: Seizures, developmental delay, and intellectual disability in affected individuals.
Potential Cancer Risk: Aneuploidy due to CEP57 dysfunction may increase tumor risk.
Expression
CEP57 is expressed in:
Brain (high in developing [cortex](/brain-regions/cortex), cerebellum)
Proliferating cells
Testis
Various tissues
Expression is highest during cell division, reflecting its role in mitosis and spindle assembly.
Therapeutic Implications
Understanding CEP57 function informs therapies for microcephaly
Cell cycle-targeted approaches may help manage aneuploidy
Gene therapy for CEP57-related disorders is under investigation