RalBP1-associated Eps domain-containing protein 2

REPS2 (RalBP1-associated Eps domain-containing protein 2) is a 660-amino acid adaptor protein that mediates ligand-dependent receptor endocytosis, particularly for EGF and insulin receptors, as part of the Ral signaling pathway (UniProt: Q8NFH8). By controlling growth factor receptor trafficking, REPS2 is thought to regulate cell survival. The protein also interacts with ASAP1 to modulate cell adhesion and migration processes.

REPS2 is broadly expressed and involved in intracellular trafficking and signal transduction. No disease associations are annotated in the UniProt record.

In Alzheimer's disease, REPS2 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂ fold-change of −0.84 across subcellular fractions (Chaparral AD proteomics). This reduction may reflect impaired growth factor signaling or endocytic dysfunction in the AD brain, potentially contributing to neuronal loss or altered cell survival pathways characteristic of the disease.