praja2 belongs to a growing family of widely expressed mammalian RING-H2 proteins with intrinsic E3 ubiquitin-ligase activity.23, 24, 25, 26 During GPCR•cAMP stimulation, praja2 ubiquitylates and degrades the inhibitory (R) subunits of PKA, sustaining downstream signals carried out by cAMP.27 In proliferating cells, praja2 promotes ubiquitin-dependent proteolysis of MOB1, a core component the tumor-suppressor Hippo cascade. Here, PJA2 is linked to neoplasm.