Ankyrin repeat and sterile alpha motif domain containing protein 1B (ANKS1B)

Ankyrin repeat and sterile alpha motif domain containing protein 1B (ANKS1B, also known as AIDA-1) is a multi-domain, predominantly brain-expressed scaffold protein critical for postsynaptic density organization and synaptic signaling[1][2][3]. It contains ankyrin repeats, SAM domains, and a phosphotyrosine binding domain, enabling interactions with synaptic proteins, most notably glutamate receptors and PSD-95[1][2]. ANKS1B is central to synaptic plasticity, trafficking of NMDA glutamate receptor subunits, and activity-dependent nuclear signaling for gene expression modulation[1][2]. Pathogenic variants cause neurodevelopmental syndromes characterized by autism, ADHD, intellectual disability, and myelination defects[4][8]. Pharmacogenomic studies link ANKS1B genetic variants to antipsychotic drug response, cognition, and several CNS and cancer phenotypes[6][9]. It also interacts with the amyloid precursor protein, tying it to Alzheimer’s disease mechanisms[2][3][9]. ANKS1B has emerged as a potential therapeutic target for psychiatric and neurodevelopmental disorders, although no approved drugs specifically target its scaffolding function to date[1][4][6].

Other names

AIDA-1ANKS2EB-1EB1Cajalin-2

Modulation of postsynaptic density and synaptic plasticity (impacts NMDA receptor and glutamatergic signaling)[1][2][4]; Influences transport and localization of NMDA receptor subunit GluN2B[2]; Potential role in amyloid precursor protein (APP) processing (possible impact in Alzheimer’s disease)[2][3][9]