Cytoskeleton-associated protein 4

Cytoskeleton-associated protein 4 (CKAP4) is a 602-amino acid anchoring protein that mediates the attachment of the endoplasmic reticulum to microtubules, thereby regulating cellular cytoskeletal architecture (UniProt: Q07065). The protein also functions as a high-affinity epithelial cell surface receptor for the sialoglycopeptide APF/antiproliferative factor, transducing antiproliferative signaling within cells. CKAP4 is expressed broadly in human tissues and has no recorded disease associations in UniProt.

In Alzheimer's disease, CKAP4 shows consistent downregulation in post-mortem AD brain tissue compared to age-matched controls. Analysis of four subcellular fractions from a TMT-labeled proteomic study detected the protein in one fraction with a mean log₂ fold-change of −0.60 (Chaparral AD proteomics). This modest but directional decrease suggests reduced ER-to-microtubule anchoring capacity in the AD brain, which may contribute to cytoskeletal disruption and cellular stress observed in neurodegeneration. The functional relevance of CKAP4 downregulation to AD pathology warrants further investigation.