It has been demonstrated that Renalase is a secreted flavin that acts as a survival factor after ischemic and toxic damage, signaling through the plasma calcium channel PMCA4b and activating the PI3K/AKT and MAPK pathways, with significantly increased expression in primary melanoma and CD163(+) tumor-associated macrophages, which in turn regulates the metabolic reprogramming of tumors and TAM (34). This evidence concerns the gene AKT1 and neoplasm.