NCK-interacting protein with SH3 domain

NCKIPSD (NCK-interacting protein with SH3 domain) is a 722-amino-acid protein that regulates actin cytoskeletal dynamics and cell adhesion (UniProt: Q9NZQ3). It promotes stress fiber formation via interaction with diaphanous-related formin DRF1, stimulates N-WASP-mediated ARP2/3 complex activation independently of CDC42, and plays roles in microspike formation, sarcomere maintenance, and angiogenesis. The protein is implicated in actin polymerization and myofibril assembly.

NCKIPSD localizes to multiple subcellular compartments and participates in cytoskeletal organization pathways relevant to neuronal morphology and synaptic function. No curated disease associations are listed in UniProt for this protein.

In Alzheimer's disease, NCKIPSD is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.51; Chaparral AD proteomics). This reduction was detected across subcellular fractions in a TMT-labeled proteomics study of human tissue. The downregulation of a protein central to actin dynamics may reflect compromised cytoskeletal integrity and reduced synaptic structural plasticity characteristic of AD neurodegeneration.