AGAP2, also known as Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2, is a protein belonging to the Arf GAP (GTPase activating protein) protein family. These proteins act as GTPase switches for Arfs (Ras superfamily members), thus being involved in signaling regulation. AGAP2 has GTPase activity and participates in multiple cellular functions like membrane trafficking, actin cytoskeleton remodeling, apoptosis, cell survival, migration, and receptor trafficking [1].

AGAP2's increase is associated with pathologies such as cancer and fibrosis. In liver fibrosis, its expression modulates some of the pro-fibrotic effects of Transforming growth factor beta-1 (TGF-β1) [1]. In clear cell renal cell carcinoma (ccRCC), AGAP2 is upregulated compared to normal tissues, and its higher expression is related to clinical cancer stages, TNM stages, pathologic stages, and status. Prognostic analysis shows that its overexpression is associated with reduced overall survival in KIRC, while it may improve the OS in some other cancers. GO and KEGG analysis indicate AGAP2-related genes are linked to T cell activation, immune activity, and PD-L1 expression and PD-1 checkpoint pathway, and AGAP2 is significantly associated with multiple types of immune cells and affects immune cell infiltration levels [3]. In phagocytes, AGAP2 localizes at actin-rich phagocytic cups and increases Fcγ receptor-mediated phagocytosis. The GAP domain of AGAP2, but not its GAP activity, is important in FcγR-dependent uptake of opsonized particles [2].

In conclusion, AGAP2 is a multi-functional protein involved in various cellular signaling pathways and biological functions. Its dysregulation is associated with diseases like cancer and fibrosis. Studies on AGAP2, especially through gene-based models in different disease contexts, help in understanding disease mechanisms and could potentially lead to new therapeutic strategies for these diseases.