ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1)

ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) is a multi-span transmembrane protein localized to the endoplasmic reticulum, where it plays a key role in shaping ER structure and promoting reticulophagy (ER-phagy) by forming complexes with ER-phagy receptors such as FAM134B. Mutation or loss of ARL6IP1 impairs ER dynamics, causes defective ER-phagy, and is associated with progressive neurodegeneration, most notably hereditary spastic paraplegia type 61 (SPG61). ARL6IP1 also negatively regulates apoptosis, likely by modulating caspase-9 activity, and influences glutamate transport by interacting with SLC1A1. The small molecule conophylline has been shown to bind ARL6IP1 and modulate its function, indicating potential for therapeutic exploration. No commonly used marketed drugs target ARL6IP1 in clinical practice as of 2025.

Other names

Apoptotic regulator in the membrane of the endoplasmic reticulumARL6IPARMERKIAA0069SPG61Aip-1AIP1ARL-6-interacting protein 1ARF like GTPase 6 interacting protein 1ADP-ribosylation factor GTPase 6 interacting protein 1

Conophylline (CNP) binds directly to ARL6IP1, modulating its biological activity and providing potential anti-apoptotic effects