The FAM3 gene family is a novel cytokine-like gene family, which includes four members designated as FAM3A, FAM3B, FAM3C, and FAM3D. FAM3A is a secreted protein belonging to the FAM3 family of four alpha -helix bundle cytokines. It is expressed in multiple tissues. Mature human FAM3A shares approximately 93% amino acid sequence identity with the mouse and rat protein.FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. FAM3A activated Akt through the p110α catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca2+ levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM).