Arl6ip5, also known as JWA, is an endoplasmic reticulum-localized protein belonging to the prenylated rab-acceptor-family. It plays important roles in multiple biological processes such as exocytic protein trafficking, glutathione metabolism, and is associated with pathways like autophagy, apoptosis, and ER stress response. It has significant biological importance in various tissues and diseases [4,5].

In ovarian carcinoma, overexpression of ARL6IP5 decreased cellular proliferation, invasion, etc., and reduced cisplatin-resistance by suppressing DNA repair and promoting apoptosis, while knockdown had the opposite effects. ARL6IP5 expression was associated with chemotherapeutic response and prognosis [1].

In Parkinson's disease, its level decreases in the brain, and overexpression reduces α-synuclein aggregate burden by inducing autophagy via preventing ubiquitination and degradation of ATG12 [2].

In prion disease, overexpression of ARL6IP5 overcomes ER stress and induces reticulophagy to reduce the PRNP/PrPSc burden [3].

In bone, Arl6ip5 knockout mice show decreased bone mineral density. Osteoblast proliferation and differentiation are impaired in Arl6ip5-knocked-down and deficient primary osteoblasts, and Arl6ip5 insufficiency in osteoblasts enhances osteoclastogenesis [5].

In conclusion, Arl6ip5 has diverse biological functions including regulation of apoptosis, autophagy, and bone metabolism. Gene knockout models, especially in the context of ovarian carcinoma, Parkinson's disease, prion disease, and bone-related studies, have significantly contributed to understanding its role in these disease areas. These findings provide potential directions for further research and therapeutic development related to Arl6ip5-associated diseases.