RAB42 is a member of the Ras family small GTPases that regulates intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound forms to recruit downstream effectors for vesicle formation, movement, tethering, and fusion. 1 RAB42 displays slow prenylation kinetics compared to other Rab GTPases, which may affect its membrane targeting efficiency. 1 In cancer contexts, RAB42 is significantly upregulated and associated with poor prognosis across multiple tumor types. 2 RAB42 expression correlates positively with immune cell infiltration and immune checkpoint genes, functioning as a predictive biomarker for immunotherapy efficacy. 2 In hepatocellular carcinoma, RAB42 silencing downregulates PD-L1 expression through inhibition of the E2F signaling pathway, thereby reducing immune escape. 3 RAB42 was identified as a risk hub gene in glioma prognosis models and associates with increased T cell exhaustion and immunosuppressive cell infiltration. 4 Pan-cancer analysis reveals that genetic and epigenetic factors, including TP53-driven alterations, DNA methylation, and super-enhancers, regulate RAB42 overexpression in tumors. 2 RAB42 represents a promising diagnostic, prognostic, and therapeutic target for cancer immunotherapy.