On the tubular ER membrane, RAB22A/TMEM33/RTN4 assembly promotes RTN4 oligomerization, which generates RTN4 cluster-enriched microdomains. ER remodeling resulted from RTN4 microdomains induces the bud scission of membrane-bound RTN4 vesicles. ATG9A transports RTN4 vesicles for homotypic fusion, leading to the formation of the early IM, which serves as phagophore of RTN4 noncanonical autophagosomes. Finally, the secretory ER-phagy-derived RTN4 noncanonical autophagosomes are secreted via Rafeesomes as R-EVs marked by TMEM33.
