Vps29, a component of the retromer complex, is crucial for endosomal recycling. The endolysosomal system, where Vps29 functions, is a dynamic membrane network for degradation and recycling. Vps29 acts as a central scaffold, coordinating the assembly of retrieval complexes with regulatory components to balance degradation and recycling of cargo molecules in endosomes [1].

In functional studies, Vps29 has been found to have diverse impacts. Loss-of-function experiments, such as a genome-wide CRISPR screen, showed that Vps29 is required for the infection of several coronaviruses including HCoV-OC43 and SARS-CoV-2, as well as ebolavirus, while it has an enhancing effect on influenza A virus infection. Deficiency in Vps29 causes changes in endosome morphology, acidity, and attenuates endosomal protease activity, entrapping incoming coronavirus particles [2]. In Drosophila, Vps29 is dispensable for embryogenesis but essential for retromer function in aging adults, regulating synaptic transmission, survival, and locomotion. In Vps29 mutants, retromer is mislocalized, and progressive endolysosomal dysfunction occurs with aging [4]. A CRISPRi screen in a human iPSC-derived neuronal model identified Vps29 as a genetic modifier of seeding-induced Tau propagation in tauopathy [3]. Bioinformatics and Mendelian randomization analysis indicated that Vps29 is overexpressed in hepatocellular carcinoma (HCC), is an independent prognostic factor, and a risk factor for HCC occurrence and progression [5].

In conclusion, Vps29 is essential for endosomal recycling and plays significant roles in various biological processes and disease conditions. Studies using different genetic models, like loss-of-function screens and Drosophila models, have revealed its importance in viral infections, neurodegenerative diseases, and cancer. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.