Reticulon-3 (RTN3)

Reticulon-3 (RTN3) is a member of the reticulon family of endoplasmic reticulum (ER) membrane proteins, highly expressed in neuroendocrine tissues[3]. RTN3 plays a critical role in shaping and maintaining ER tubules and acts as a selective receptor (especially its long isoform RTN3L) in ER-phagy, the autophagic degradation pathway dedicated to ER tubule turnover[1]. RTN3 exerts its autophagy receptor function via multiple (six) LC3-interacting regions (LIRs), enabling it to bind autophagy modifiers and deliver ER fragments to lysosomes for degradation during autophagy[1]. Additionally, RTN3 interacts with and negatively regulates beta-amyloid converting enzyme 1 (BACE1), thereby reducing amyloid-beta production, implicating it in Alzheimer's disease pathology[3]. Variants and altered expression of RTN3 have been linked to neurodegenerative diseases and neuroinflammation[3]. No direct drugs target RTN3, nor are there established clinical biomarkers or safety concerns associated with modulation of the protein. RTN3 is not a classical drug target like a receptor, enzyme, or ion channel, but its activity and pathways afford mechanisms that may be exploited in disease contexts, particularly neurodegeneration[1][3].

Other names

Reticulon-3RTN3ASYIPNSPL2HAPNSP-like protein 2NSP-like protein IINSPLIIRTN3-A1Homolog of ASY proteinNeuroendocrine-specific protein-like 2Neuroendocrine-specific protein-like IIASY interacting protein