Receptor expression-enhancing protein 2

REEP2 (Receptor expression-enhancing protein 2) is a 252-amino-acid protein involved in endoplasmic reticulum (ER) network formation, shaping, and remodeling. It may also enhance cell surface expression of odorant receptors (UniProt: Q9BRK0). The protein is broadly expressed across tissues involved in neuronal and sensory function.

REEP2 is associated with spastic paraplegia types 72A and 72B (SPG72A/SPG72B), progressive neurodegenerative disorders characterized by lower-limb weakness and spasticity beginning in early childhood with preserved cognition and speech (UniProt: Q9BRK0). These hereditary conditions highlight REEP2's role in neuronal maintenance and axonal function.

In Alzheimer's disease, REEP2 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.35 across analyzed subcellular fractions (Chaparral AD proteomics). This reduction may reflect ER stress or altered membrane trafficking dysfunction characteristic of AD pathology, though the functional consequence requires further investigation.