Neurobeachin

Neurobeachin (NBEA) is a large cytoplasmic anchoring protein that binds type II regulatory subunits of protein kinase A and targets them to membranes and associated cellular structures (UniProt: Q8NFP9). The protein functions in subcellular localization of signaling complexes, with potential roles in cytoskeletal and organellar organization. NBEA is expressed in neurons and has established relevance to neurodevelopmental function.

Mutations in NBEA cause neurodevelopmental disorder with or without early-onset generalized epilepsy (NEDEGE, MIM 619157), an autosomal dominant condition characterized by developmental delay, intellectual impairment, speech deficits, and behavioral abnormalities including autism spectrum features, attention deficits, and seizures typically appearing in infancy or early childhood (UniProt: Q8NFP9).

In Alzheimer's disease, NBEA is downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.50), as measured by quantitative proteomics across subcellular fractions (Chaparral AD proteomics). This reduction may reflect compromised PKA anchoring and synaptic signaling dysfunction in the AD brain, linking the protein's neurodevelopmental role to potential mechanisms of neurodegeneration.