In summary, in the present work we demonstrated that in lung cancer and mesothelioma cells, RBL1/p107 levels and phosphorylation are modulated by a complex network of functional interactions involving Ca2+-dependent signaling, CaMKs, calpain and their ability to directly or indirectly regulate the cell cycle, pointing out a substantial difference with the mechanisms regulating RBL2/p130 stability. The gene discussed is RBL1; the disease is mesothelioma.