Snx9, or sorting nexin-9, is a multifunctional protein involved in fundamental cellular activities. It participates in endocytosis, coordinating membrane trafficking and remodeling with actin dynamics [2,5]. Snx9 binds strongly to dynamin, recruits it to endocytosis sites, modulates the membrane for endocytic vesicle formation, stimulates dynamin's GTPase activity for scission, and activates N-WASP to coordinate actin polymerization with vesicle release [2]. It is also involved in pathways like T-cell activation and GPCR endocytosis [3,4].

In CD8 T cells, gene knockout experiments revealed that deletion of Snx9 alleviates T-cell exhaustion. It decreases PLCγ1, Ca2+, and NFATc2-mediated T-cell signaling, reduces expression of NR4A1/3 and TOX, enhances memory differentiation and IFNγ secretion of adoptively transferred T cells, and improves the anti-tumor efficacy of human chimeric antigen receptor T cells in vivo [1]. In Autosomal Dominant Polycystic Kidney Disease (ADPKD), Snx9 expression is downregulated. Ectopic expression of Snx9 inhibits ADPKD cell proliferation and cyst formation by interacting with YAP, increasing its phosphorylation, and inhibiting Hippo target gene expression [6].

In conclusion, Snx9 is crucial for multiple cellular processes such as endocytosis, T-cell function, and cell proliferation regulation. Gene knockout models have been instrumental in uncovering its role in diseases like T-cell exhaustion-related cancers and ADPKD, providing potential therapeutic targets for these conditions.