Moreover, we established the functional association between RGS20-regulated PI3K/AKT pathway activation and malignant progression of PC, as the overexpression of constitutively activated PI3K p110α, rather than its kinase-dead mutant, rescued cell proliferation, and cell migration/invasion attenuated by RGS20 knockdown in PC cells. Here, RGS20 is linked to pachyonychia congenita.