Actin-like protein 6B

Actin-like protein 6B (ACTL6B) is a 426-amino-acid protein that functions as a component of the neuron-specific BAF (nBAF) chromatin remodeling complex (UniProt: O94805). It mediates transcriptional activation and repression through ATP-dependent alterations of DNA-nucleosome topology. ACTL6B is essential for neuronal maturation and dendritic outgrowth, playing a critical role in the developmental switch from neural progenitor cells to postmitotic neurons by replacing its paralog ACTL6A within chromatin remodeling complexes.

ACTL6B is expressed in neurons and functions within the nBAF complex alongside CREST to regulate genes essential for dendrite growth and neural development. Mutations in ACTL6B are associated with severe neurodevelopmental disorders, including developmental and epileptic encephalopathy 76 (DEE76) and intellectual developmental disorder with severe speech and ambulation defects (IDDSSAD), both characterized by global developmental delay and neurological impairment (UniProt: O94805).

In Alzheimer's disease, ACTL6B is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.57 (Chaparral AD proteomics). This reduction may reflect compromised chromatin remodeling capacity and impaired neuronal function in the AD brain.