VPS18 is a core component of the CORVET and HOPS membrane tethering complexes that plays essential roles in vesicle-mediated protein trafficking and cellular homeostasis. As part of these complexes, VPS18 facilitates endosomal fusion events, including the conversion of Rab5-positive early endosomes to Rab7-positive late endosomes, and mediates fusion of autophagosomes and endosomes with lysosomes 1. The protein contains a C-terminal RING domain that directly interacts with VPS41 to recruit it to the HOPS complex, enabling proper complex assembly 1. VPS18 also functions as an E3 ubiquitin ligase, regulating multiple signaling pathways including Wnt, estrogen receptor, and NFκB through protein ubiquitination 2. In disease contexts, VPS18 serves as a tumor suppressor in lung cancer by promoting EGFR degradation and suppressing ERK-MAPK signaling 3, while also maintaining phagosomal membrane integrity during Mycobacterium tuberculosis infection 4. VPS18 deficiency severely impairs neutrophil development through disrupted vesicle dynamics, autophagosome accumulation, and increased apoptosis, leading to neutropenia in both mouse models and human patients 5. Additionally, VPS18 regulates PD-L1 trafficking and stability, influencing immune checkpoint responses in cancer 6.