REEP1 (receptor expression-enhancing protein 1) is a membrane-shaping protein that plays critical roles in endoplasmic reticulum (ER) structure and neuronal maintenance. REEP1 generates membrane curvature to create ER-derived vesicular compartments that cycle back to the ER through atlastin-mediated fusion 1. The protein is involved in ER morphogenesis and remodeling, and contributes to microtubule cytoskeleton regulation 2. Mutations in REEP1 that compromise curvature generation relocalize the protein to the bulk ER and can retain wild-type proteins there through dominant-negative effects 1. REEP1 mutations are associated with hereditary spastic paraplegia (HSP) type 31 and distal hereditary motor neuropathy 34. In HSP cohort studies, REEP1 represents more than 1% of cases and structural variants account for a significant proportion of pathogenic mutations 3. The protein belongs to the REEP1-4 subfamily and is involved in ER tubular network organization 5. Disease-causing mutations appear to disrupt the protein's membrane curvature-generating function, leading to neurodegenerative phenotypes characterized by motor neuron dysfunction 1.