Cytoskeleton-associated protein 5

Cytoskeleton-associated protein 5 (CKAP5) is a microtubule plus-end-binding protein that regulates microtubule dynamics and organization (UniProt: Q14008). It functions as a processive microtubule polymerase, promoting cytoplasmic microtubule nucleation and elongation. CKAP5 plays a critical role in organizing spindle poles and protecting kinetochore microtubules from depolymerization during mitosis. It operates as part of the TACC3/ch-TOG/clathrin complex, which stabilizes kinetochore fibers and maintains their mechanical tension.

CKAP5 is involved in centrosome assembly and organization across multiple cellular contexts. The protein enhances kinetochore-tip microtubule attachments through interactions with the NDC80 complex, contributing to proper chromosome segregation during cell division.

In Alzheimer's Disease, CKAP5 shows ambiguous regulation direction across subcellular fractions in human post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.27 across two measured fractions, indicating modest overall downregulation, though direction varies by subcellular compartment. Given microtubule dysfunction's known role in neurodegeneration and tau pathology, altered CKAP5 expression may contribute to cytoskeletal disruption in AD.