Gdi2, also known as GDP Dissociation inhibitor 2, is a crucial regulator that maintains cellular homeostasis by regulating Rab GTPases involved in vesicular transport [4]. It plays a significant role in multiple biological processes, such as embryonic development, apoptosis regulation, and immune responses [4]. Perturbations in its function are associated with various diseases, especially cancers [4]. Genetic models, like knockout mouse models, are valuable for studying Gdi2's functions.

In gene knockout studies, complete loss of Gdi2 leads to early embryonic lethality, with developmental retardation apparent at E10.5-E14.5, and no viable Gdi2 -/- embryos after E14.5 due to extensive cell death and apoptosis [1]. In the 5xFAD mouse model of Alzheimer's disease, neuron-specific knockout of GDI2 significantly ameliorates cognitive impairment, reduces senile plaques, and astrocyte activation, suggesting GDI2 may regulate Aβ production by modulating APP intracellular transport [2]. In prostate cancer, knocking down GDI2 suppresses cell proliferation and promotes apoptosis via the p75NTR signaling pathway [3]. Silencing GDI2 in colorectal cancer cells inhibits their proliferation, migration, and invasion through activation of the p53 signaling pathway [5].

In conclusion, Gdi2 is essential for embryonic development and is involved in apoptosis regulation. Its dysregulation is linked to cancer and Alzheimer's disease. Gene knockout mouse models have been instrumental in revealing Gdi2's role in these biological processes and disease conditions, providing potential therapeutic targets for related diseases.