To complete the GTP/GDP cycle of these ubiquitous Rab GTPases, GDF proteins direct soluble GDP-Rab GTPase complexes to the membranes of target organelles. GDP-Rab GTPase, which is trapped in the membrane of an organelle, needs to be released from the membrane in order to complete the cycle. This can only be done with the help of GDI. This research established that the F13 protein had the GEF, GAP, Dynamin, and PPM domains necessary to accomplish the viral membrane-cellular membrane fusion process. Nonetheless, the GDI-associated domain and binding domain are absent in the F13 protein of the monkeypox virus E protein. It is possible that F13 proteins can function fine without GDF and GDI proteins. The Monkeypox virus F13 protein finishs membrane targeting via domains including GP120 and PI3K. Therefore, the roles of GDF proteins can be handled by GP120 and PI3K proteins instead. The membrane fusion process becomes highly unstable if the F13 protein contains a domain that can interact with GDI, increasing the likelihood of interrupting the GTP/GDP cycle. It appears that the F13 protein of the monkeypox virus may not need GDF/GDI proteins to complete its GTP/GDP cycle.