TUBA4A: The Tale of an Unconventional Tubulin.

Microtubules are highly adaptable cytoskeletal polymers whose dynamic nature supports a broad spectrum of cellular activities. Their dynamic behavior is regulated by an intricate network of factors, including tubulin isotypes and post-translational modifications. Together, these elements shape the properties of microtubules in response to both intrinsic and extrinsic cues. Within this regulatory landscape, the "tubulin code" has been proposed as a conceptual framework to explain how subtle molecular variations shape context-specific microtubule functions. Among mammalian α-tubulin isotypes, TUBA4A is characterized by the unique C-terminal tail, distinct biochemical behaviors, enriched expression in multiple tissues (e.g., in the central nervous system) and emerging roles in neurodegeneration. This review summarizes the molecular and physiological features of TUBA4A, highlights its potential contributions to normal neuronal function and neurological disorders, and offers perspectives for future studies.