Adenylyl cyclase-associated protein 2

Adenylyl cyclase-associated protein 2 (CAP2) is a 477-amino acid cytoplasmic protein that regulates actin polymerization (UniProt: P40123). It is involved in controlling cytoskeletal dynamics through interactions with actin filaments. CAP2 has been associated with dilated cardiomyopathy type 2I (CMD2I), a severe autosomal recessive disorder characterized by ventricular dysfunction and congestive heart failure (UniProt: P40123).

In Alzheimer's Disease, CAP2 is consistently down-regulated in post-mortem human brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.55 across quantified subcellular fractions (Chaparral AD proteomics). This reduction was measured via TMT-labeled, data-dependent acquisition proteomics across four subcellular compartments (P2, P3, S2, S3). The decreased abundance of this actin-regulatory protein may reflect impaired cytoskeletal remodeling capacity in AD-affected neurons, potentially contributing to synaptic dysfunction or neurodegeneration.