Tubulin is the structural component of microtubules, which are highly dynamic polymers involved in several cellular functions such as mitosis, locomotion, and intracellular transport.

Humans have multiple isoforms of α, β, and γ-tubulins, which possess specific tissue and development distributions. Pathogenic variants in 8 of these tubulin genes cause a wide and heterogeneous class of pathological conditions collectively known as tubulinopathies. Tubulinopathies have been historically associated to a broad spectrum of congenital and non- progressive disorders of brain neurodevelopment that mostly include lissencephaly, polymicrogyria and microcephaly. Nevertheless, in recent years an increasing number of tubulin mutations have also been linked to neurodegenerative profiles such as ALS, CFEOM and polyneuropathy, while a small number have been associated to non-neurological conditions such as bleeding disorders and infertility, thus making it necessarily a more revised redefinition of the phenotypical spectrum of these conditions.

Although neurodevelopmental tubulinopathies have a great clinical heterogeneity, common cortical malformation patterns have been identified; these hallmarks can be recognized by neuroimaging even during the fetal period, allowing an early diagnosis of these conditions.
Conversely, neurodegenerative, and non-neurological tubulinopathies represent an emerging and clinically poorly characterized subclass of tubulinopathies, and no clear hallmarks that favor their differential diagnosis have been identified so far.
Moreover, the lack of functional studies directed to understanding the effect of the different tubulin mutations with the aim of creating genotype-phenotype correlations of tubulinopathies,
makes our knowledge about the pathogenesis of these diseases, fragmentary, preventing the identification of molecular targets to develop therapeutic strategies and/or factors that may influence the disease course.

This Research Topic aims to increase our awareness about clinical phenotypes and genetic causes of tubulinopathies, and at the same time, to advance our knowledge about molecular pathways that are disrupted by tubulin mutations to create genotype-phenotype correlations and finally identify potential molecular targets for therapies.

We will consider original research articles, comprehensive reviews, and perspectives in line with the Topic. More specifically, submissions may be related to (but not limited to) the following topics:

i) Genetic and clinical studies that expand the phenotypical and mutational spectrum of tubulinopathies
ii) Identification of clinical hallmarks to further improve the differential diagnosis of tubulinopathies
iii) Functional studies aimed at identifying common molecular pathways that are differentially affected by tubulin mutations related to neurodevelopmental, neurodegenerative, and non-neurological tubulinopathies
iv) Potential for novel therapeutic perspectives for the treatment of tubulinopathies.

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Frontiers in Cellular Neuroscience

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