Caskin-1

Caskin-1 (CASKIN1) is a scaffolding protein that functions as a linker between CASK and downstream intracellular effectors, facilitating signal transduction and protein–protein interactions (UniProt: Q8WXD9). The protein is 1,431 amino acids in length and is expressed in human tissues, though specific tissue distribution details are not annotated in available records.

In the context of Alzheimer's Disease, Caskin-1 shows decreased abundance in human post-mortem AD brain tissue compared to age-matched controls. Analysis of subcellular fractions (P2, P3, S2, S3) using TMT-labeled tandem mass spectrometry revealed a mean log₂ fold-change of −0.304, indicating modest downregulation (Chaparral AD proteomics). This reduction was consistent across the measured fractions, suggesting a relatively stable decrease across cellular compartments rather than selective loss in one fraction.

The functional significance of this downregulation remains unclear, though loss of CASKIN1-mediated scaffolding could potentially affect synaptic organization or calcium signaling pathways known to be disrupted in neurodegeneration. No disease associations are documented in UniProt curated records for this protein.