ARL6IP5 is a multifunctional endoplasmic reticulum (ER) membrane protein that serves as a critical regulator of cellular stress responses and protein degradation pathways. The protein functions as an ER membrane-shaping protein through its conserved PRA1 domain, inducing ER tubule formation and membrane constriction 1. ARL6IP5 acts as a key autophagy inducer by preventing ubiquitination and degradation of ATG12, thereby promoting α-synuclein clearance in neurodegenerative diseases 2. In response to ER stress, ARL6IP5 is upregulated and induces reticulophagy through Ca2+-mediated AMPK activation and interactions with CALCOCO1 and LAMP1, effectively reducing misfolded prion protein burden 3. The protein demonstrates tumor suppressor properties in ovarian carcinoma by suppressing DNA repair pathways while promoting apoptosis, thereby reducing cisplatin resistance 4. ARL6IP5 expression decreases with age and in Parkinson's disease, and its levels are associated with renal function decline through altered DNA methylation patterns 5. Additionally, ARL6IP5 interacts with ARL15 in adipocyte differentiation processes 6 and serves as a prognostic biomarker in acute myeloid leukemia 7.