Ras-associated and pleckstrin homology domains-containing protein 1

RAPH1 (Ras-associated and pleckstrin homology domains-containing protein 1) is a 1250-amino acid signaling protein that mediates localized membrane signals and regulates lamellipodial dynamics at the cell membrane (UniProt: Q70E73). It negatively regulates cell adhesion, suggesting a role in controlling dynamic cell–cell and cell–matrix interactions. The protein functions in processes requiring rapid cytoskeletal reorganization and membrane signal transduction.

RAPH1 lacks documented disease associations in the UniProt knowledge base, but proteomic analysis of human post-mortem Alzheimer's disease brain tissue has identified dysregulation of this protein (Chaparral AD proteomics). In subcellular fractionation experiments comparing AD brain to age-matched controls, RAPH1 was consistently downregulated with a mean log2 fold-change of −0.46 across the measured fractions. This reduction in RAPH1 protein abundance in AD brain tissue may reflect altered membrane signaling or adhesion dynamics relevant to neurodegeneration, though the specific functional consequences of this downregulation require further investigation.